Process for preparing dihalovinylcyclopropanecarboxylates

ABSTRACT

Novel synthesis of dihalovinylcyclopropanecarboxylates, including potent insecticides, are described. The processes begin with the reaction between an alkenol and an orthoester to produce a γ-unsaturated carboxylate, followed by the catalyzed addition of a carbon tetrahalide to the double bond and dehydrohalogenation to produce a cyclopropane derivative.

This application is a continuation of application Ser. No. 507,998,filed June 27, 1983, now U.S. Pat. No. 4,833,266, which is acontinuation of application Ser. No. 160,540, filed June 18, 1980, nowabandoned, which is a continuation of application Ser. No. 606,807,filed Aug. 22, 1975, now U.S. Pat. No. 4,681,953.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to a new process for preparing organic compoundscontaining the cyclopropane ring system, particularly substitutedcyclopropanes having utility as pyrethroid insecticides or asintermediates in the preparation of pyrethroid insecticides, and to newcompositions of matter useful in the practice of this process.

2. Description of the Prior Art

The class of pyrethroid insecticides includes both natural and syntheticmembers. The active natural products are extracted from the blossoms ofpyrethrum flowers (Chrysanthemum cinerariaefolium) grown mainly in EastAfrica. The composition of the extracts has been elucidated bycontinuing the classical work of Staudinger [Helv. Chim. Acta, 7, 390(1924)]. Harper [J. Chem. Soc., 892 (1946)], LaFarge et al. [J. Am.Chem. Soc., 69, 2932 (1947)], Godin et al. [J. Chem. Soc. (C), 3321(1966)] as well as Crombie et al. [Chem. & Ind., 1109 (1954)]contributed to proving that the extracts comprise at least six closelyrelated vinylcyclopropanecarboxylates: pyrethrin I, pyrethrin II,cinerin I, cinerin II, jasmolin I and jasmolin II. The most importantnatural pyrethroid is pyrethrin I. ##STR1## The structures of the otherfive components display variations in the portions of the moleculeindicated by the arrows. In cinerin II and jasmolin II the dimethylvinylgroup at the 2-position becomes (methyl) (carbomethoxy)vinyl; while inthe cinerins the pentadienyl side chain in the alcohol moiety is2-butenyl; in the jasmolins, 2-pentenyl.

In addition to optical isomerism, the pyrethroids display geometricalisomerism in that the hydrogen atoms at the 1 and 2 positions of thecyclopropane ring may be in either a cis or a trans relationship withrespect to each other as illustrated in the drawing of the pyrethrin Imolecule. The natural pyrethrin extracts comprise the trans forms and itis known that the trans isomers are more active. It is believed thatthere are two important centers in the pyrethroid structure whichespecially affect insecticidal activity, namely the substituted vinylgroup in the acid moiety and the unsaturated side chain in the alcoholportion of the molecule. The vinyl group is believed to be the site formetabolic attack and detoxification by the insect; whereas the nature ofthe alcohol moiety is believed to influence the photooxidative stability[Elliott, Chem. & Ind., 978 (1974)].

With the discovery of the structure of the natural pyrethroids andextensions by Campbell et al. [J. Chem. Soc., 283 (1945)] of the workbegun by Staudinger, it has been possible to produce syntheticpyrethroids.

Until recently, 1,1,1-trichloro-2,2-(bis-p-chlorophenyl)ethane (DDT) and1,2,3,4,5,6-hexachlorocyclohexane (BHC) were widely used asinsecticides. However, in view of the resistance of these materials tobiodegradation and their persistence in the environment, newinsecticides producing less environmental harm have been sought.Pyrethroids have long been of interest because they are active against awide range of insect species, they display relatively low toxicitytoward mammals, and they do not leave harmful residues. For example,pyrethrin I is more than 100 times as potent toward mustard beetles(Phaedon cochleariae) as DDT, but only 1/4-1/2 as toxic toward rats[Elliott et al., Chem. & Ind., 978 (1974); Nature, 244, 456 (1973);Chemical Week, Apr. 12, 1969, p. 57].

Although they possess a number of desirable characteristics, the naturalpyrethroids undergo rapid biodegradation, they have poor photooxidativestability, their availability is uncertain, and it is costly to extractand process them. For a number of years efforts have been underwayaround the world to produce synthetic pyrethroid insecticides whichwould overcome these disadvantages. A notable recent development was thediscovery of a dihalovinylcyclopropanecarboxylate (Structure II) havinga toxicity toward insects more than 10,000 times greater than that ofDDT, with an oral toxicity toward mammals similar to pyrethrin I[Elliott et al., Nature, 244, 456 (1973)]. Although Structure II, inwhich the alcohol moiety is 5-benzyl-3-furylmethyl, does not haveexceptional photooxidative stability, Elliott et al. discovered that3-phenoxybenzyl analogs (Structure III where X is halogen) wereremarkably resistant to photooxidative degradation [Nature, 246, 169(1973), Belgian Patents Nos. 800,006 and 818,811].

The objects of this application are to present processes for thesynthesis of pyrethroids in which the cyclopropanecarboxylic acid moietycontains a dihalovinyl group in the 2 position and to describe novelcompositions of matter useful in the practice of these processes.Accordingly, processes of this invention lead to esters of such acidswhich either are or may be converted readily into pyrethroidinsecticides. The major advantage of this invention is to provide aconvenient synthetic route to pyrethroids of the type represented byStructures II and III.

The early synthetic pyrethroids were compounds in which only the alcoholportion of the ester structure was varied. Synthetic pyrethroidsrepresenting this type of variation include allethrin and resmethrinwhich both contain the dimethylvinyl group of pyrethrin I, but in whichthe alcohol is allethrolone or 5-benzyl-3-furylmethyl alcoholrespectively. Like the natural products, these pyrethroide degraderapidly in air and light [Elliott et al., Nature, 246, 169 (1973)].Processes for preparing such pyrethroids generally have begun withchrysanthemic acid, obtained either by the hydrolysis of naturalpyrethroids or by the method of Staudinger [Helv. Chim. Acta, 7, 390(1924)].

Only in recent years has the cyclopropanecarboxylic acid moiety,especially the vinyl group thereof, been modified synthetically. Priorto the present invention, the known methods for varying the nature ofthe substituents occupying the 2 position in the cyclopropane ringincluded the following:

(1) Chrysanthemic acid or a naturally occurring chrysanthemate may besubjected to ozonolysis to produce caronaldehyde [Farkas et al., Coll.Czech. Chem. Com., 24, 2230 (1959)]. The aldehyde may then be treatedwith a phosphonium or sulfonium ylide in the presence of a strong base,followed by hydrolysis [Crombie et al., J. Chem. Soc. (C), 1076 (1970);Brit. Patent No. 1,285,350]. Such a reaction sequence is shown below.##STR2## The reaction may be utilized where X is an alkyl group and alsowhere X is halogen [South African Patent No. 733,528; J. Am. Chem. Soc.,84, 854, 1312, 1745 (1962)]. The reaction has been employed to prepareethyl 2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropane-1-carboxylate, aprecursor of Structures II and III. Whereas the ylide reaction proceedsin about 80% yield, the yield of aldehyde from the oxidation istypically only about 20%. The oxidative degradation originated as a toolfor proof of structure and was never intended for large-scalepreparative use. The oxidation alone requires many hours to completebecause mild conditions must be used to minimize the possibility of aviolent oxidation of the organic compound. An overall yield of 16% maynot be unacceptable when the process is used in research, but it is muchtoo low to be of practical commercial utility. In addition, the startingmaterial is costly since, in essence, it is akin to the compound whichis being prepared.

(2) The original Staudinger synthesis of chrysanthemic acid involved thereaction of ethyl diazoacetate with 2,5-dimethylhexa-2,4-diene followedby saponification of the ester [Helv. Chim. Acta, 7, 390 (1924)].Carbene addition to an unsaturated carbon-carbon linkage has become ageneral reaction for the preparation of the cyclopropane ring system[Mills et al., J. Chem. Soc., 133 (1973), U.S. Pat. Nos. 2,727,900 and3,808,260]. Such a reaction, illustrated below, has been employed in thepreparation of pyrethroids and also ethyl2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropane-1-carboxylate, precursorof II and III [Farkas et al., Coll. Czech. Chem. Comm., 24, 2230(1959)]. In preparing the latter, the starting material may be themixture of pentenols obtained by the condensation of chloral withisobutylene. ##STR3## The conversion of the mixture of pentenols to1,1-dichloro-4-methyl-1,3-pentadiene, short of thecyclopropanecarboxylate, is reportedly only about 50%. This, coupledwith the fact that in the last step the production of the diazo esterand its handling are extremely dangerous on a large scale, seriouslylimits the utility of the process. Furthermore, it is estimated that,should a pyrethroid of Structure III become a major agriculturalcommodity, commercial production by this method of enough of thedihalovinylcyclopropanecarboxylate to satisfy the potential demand mightexhaust the world supply of zinc.

(3) Julia has described a third general method capable of allowing thesubstituents in the 2 position of the cyclopropane ring to be varied[U.S. Pat. Nos. 3,077,496, 3,354,196 and 3,652,652; Bull. Soc. Chim.Fr., 1476, 1487 (1964)]. According to this method, illustrated below, anappropriately substituted lactone is first treated with a halogenatingagent, opening the ring, followed by base-induced dehydrohalogenation,forming a cyclopropane. Even in the relatively uncomplicated case wherethe terminal substituents on the vinyl group are methyl and the productis ethyl chrysanthemate, the yield is only 40%. ##STR4##

Moreover, lactones of special interest, such as3-(β,β-dichlorovinyl)-4-methyl-γ-valerolactone are not readilyavailable. Even 3-isobutenyl-4-methyl-γ-valerolactone, from which ethylchrysanthemate is made, requires a 3-step synthesis from2-methylhex-2-en-5-one, including a Grignard reaction. Grignardreactions are difficult to carry out on a large scale and, in any case,could probably not be utilized without destroying a dihalovinyl groupwere it present.

Thus, the processes taught in the prior art for varying the nature ofthe substituents occupying the 2 position in the cyclopropane ring,particularly processes for introducing a 2-dihalovinyl group, sufferfrom a number of disadvantages, the most serious of which are:

(1) The yields of cyclopropanecarboxylates are too low for practicalapplication in commerce;

(2) The starting materials are not readily available, requiringadditional synthetic steps, adding to costs and increasing the price ofthe product beyond that which the market will bear;

(3) The processes all involve at least one reaction which is difficultand dangerous to carry out on a large scale, inviting the risk of fireor explosion.

SUMMARY OF THE INVENTION

It has now been found that the serious disadvantages inherent in theprocesses of the prior art can be largely overcome by novel syntheses,which proceed in high yield, using readily available, comparativelyinexpensive starting materials, in a few safe, commercially feasiblesteps, via novel compositions of matter as intermediates, to producepyrethroids of the type represented by Structures II and III orintermediates converted readily into such pyrethroids. The syntheticsteps employed in the processes of this invention proceed in high yield;yields of 90% or higher are common. In addition,dihalovinylcyclopropanecarboxylates in which the more active transisomer ranges isomer ranges in amount from 50% to 90% can be made withalmost no variation in yield.

The novel processes of this invention are illustrated specifically bythe following chemical equations and Examples wherein, starting withreadily available 3-methyl-2-buten-1-ol and ethyl orthoacetate, eitherthe potent, persistent pyrethroid, III, or ethyl2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate, anintermediate in the preparation of III, is produced. ##STR5##

In the Examples which follow, temperatures are in degrees centigrade.Where ir spectra are given, only the frequencies of the most prominentabsorption maxima appear. Tetramethylsilane was employed as an internalstandard for the nmr spectra. In reporting the nmr data theabbreviations have the following significance: s, singlet; d, doublet;t, triplet; q, quartet; m, multiplet. Any of these abbreviations may bepreceded by b for broad or d for double, for example, d.d., doubledoublet; b.t., broad triplet.

EXAMPLE I Synthesis of 3-Phenoxybenzyl2-(β,β-Dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate A. Preparationof ethyl 3,3-dimethyl-4-pentenoate

A mixture of 0.65 g of 3-methyl-2-buten-1-ol, 2.43 g of ethylorthoacetate and 50 mg of phenol was heated at 120° with stirring. After2 hours, the temperature was increased to 140° where it was maintainedfor 20 hours. When ethanol evolution had ceased, the mixture wasdissolved in benzene to a total volume of 5 ml. Gas chromatographicanalysis of the benzene solution showed that ethyl3,3-dimethyl-4-pentenoate had been produced in 92% yield (see Example Vfor physical properties).

B. Transesterification between 3-phenoxybenzyl alcohol and ethyl3,3-dimethyl-4-pentenoate

A mixture of 374 mg of ethyl 3,3-dimethyl-4-pentenoate, 400 mg of3-phenoxybenzyl alcohol and 16 mg of sodium ethoxide in 10 ml of toluenewas heated under reflux for 24 hours, with a Dean-Stark apparatuscontaining a molecular sieve to absorb the evolved ethanol. The mixturewas neutralized by adding an anhydrous ether solution of hydrogenchloride. The neutral solution was poured into water. The ether layerwas separated, dried over magnesium sulfate, and distilled to give 520mg (70% yield) of 3-phenoxybenzyl 3,3-dimethyl-4-pentenoate, b.p.155°-158°/0.3 mm.

Analysis: Calculated for C₂₀ H₂₂ O₃ : C, 77.39; H, 7.14. Found: C,77.14; H, 7.11.

nmr δ ppm (CCl₄): 7.32-7.08 (m, 4H), 7.05-6.70 (m, 5H), 5.76 (d.d., 1H),4.92 (s, 2H), 4.96-4.70 (m, 2H), 2.22 (s, 2H), 1.08 (s, 6H).

C. Addition of carbon tetrachloride to 3-phenoxybenzyl3,3-dimethyl-4-pentenoate

A mixture of 245 mg of 3-phenoxybenzyl 3,3-dimethyl-4-pentenoate in 5 mlof carbon tetrachloride was charged to a pressure vessel, and to it wasadded 2 mg of benzoyl peroxide. The vessel was purged with argon andsealed. The sealed vessel was heated for 5 hours at 140°, then cooled,and an additional 2 mg of benzoyl peroxide was added. The vessel againwas purged, sealed and heated at 140° for 5 hours. The procedure wasrepeated twice more after which the vessel was cooled and the contentswere washed successively with water, saturated aqueous sodiumbicarbonate and water. The washed mixture was dried over magnesiumsulfate, and the solvent was removed under reduced pressure. The residuewas purified by silica gel chromatography with benzene as the elutingsolvent to give 300 mg (82% yield) of 3-phenoxybenzyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate.

Analysis: Calculated for C₂₁ H₂₂ Cl₄ O₃ : C, 54.33; H, 4.78; Cl, 30.55Found: C, 54.76; H, 4.88; Cl, 30.24

nmr δ ppm (CCl₄): 7.35-7.05 (m, 4H), 7.05-6.75 (m, 5H), 4.96 (s, 2H),4.30 (d.d., 1H), 3.30-2.80 (m, 2H), 2.57 (d, 1H), 2.26 (d, 1H), 1.15 (s,3H), 1.07 (s, 3H).

D. Simultaneous cyclization and dehydrochlorination

A solution of 200 mg of 3-phenoxybenzyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate in 1 ml of anhydroustetrahydrofuran was added dropwise to a suspension of 124 mg of sodiumt-butoxide in 5 ml of anhydrous tetrahydrofuran during which thereaction mixture was cooled in ice. After 1 hour, the mixture wasallowed to warm to room temperature and then it was heated under refluxfor 1 hour. The mixture was neutralized by the addition of an anhydrousether solution of hydrogen chloride. The neutralized mixture was pouredinto ice water and extracted with diethyl ether. The ether extract wasdried over magnesium sulfate, and the solvent was removed under reducedpressure. The residue was purified by column chromatography, using asilica gel column with benzene as the eluting solvent, to give 126 mg(75% yield) of 3-phenoxybenzyl2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate.

Analysis: nmr δ ppm (CCl₄): 6.80-6.50 (m, 9H), 6.25 (b.d, 0.5H), 5.60(d, 0.5H), 5.05 (s, 2H), 2.40-1.40 (m, 2H), 1.40-1.05 (m, 6H).

EXAMPLE II Synthesis of Ethyl2-(β,β-Dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate A. Addition ofcarbon tetrachloride to ethyl 3,3-dimethyl-4-pentenoate

To a solution of 135.2 mg (0.5 mmole) of ferric chloride hexahydrate and146.3 mg (2.0 mmoles) of n-butylamine in 2.19 g of dimethylformamidecontained in a pressure vessel was added 1.56 g (10 mmoles) of ethyl3,3-dimethyl-4-pentenoate and 4.26 g (30 mmoles) of carbontetrachloride. The vessel was sealed and heated for 15 hours at 100°.The vessel was then cooled, and the contents were dissolved in diethylether. The etheral solution was washed successively with 1N hydrochloricacid, saturated aqueous sodium bicarbonate and saturated aqueous sodiumchloride. The washed solution was dried over magnesium sulfate anddistilled to give 2.79 g (90% yield) of ethyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate, b.p. 116°/0.18 mm.

Analysis: Calculated for C₁₀ H₁₆ Cl₄ O₂ : C, 38.74; H, 5.20; Cl, 45.74;Found: C, 38.91; H, 5.07; Cl, 45.85.

nmr δ ppm (CCl₄): 4.37 (d.d., 1H), 4.07 (q, 2H), 3.40-2.85 (m, 2H), 2.40(q, 2H), 1.27 (t, 3H), 1.20 (d, 6H).

B. Simultaneous cyclization and dehydrochlorination

Into a solution of 3.1 g (10 mmoles) of ethyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate in 40 ml of absolute ethanolwas added dropwise 20 ml of an ethanol solution containing 1.5 g (22mmoles) of sodium ethoxide. The mixture was stirred at room temperaturefor 1 hour after the addition was completed, then refluxed for 1 hour.The mixture was reduced by distillation to about one-tenth its originalvolume and cooled with ice, and the residue was neutralized by theaddition of 1N hydrochloric acid. The neutral solution was extractedwith diethyl ether, and the ether extract was washed successively withsaturated aqueous sodium bicarbonate and saturated aqueous sodiumchloride. After drying over magnesium sulfate, the solution wasdistilled to give 2.12 g (89% yield) of ethyl2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate, b.p. 77°/0.3mm (see Example III for physical properties).

The novel processes just described specifically are capable of generalapplication as represented by the following chemical equations: ##STR6##

In defining the substituent R groups, the term "lower", modifying suchexpressions as alkyl, alkene, alkoxy, etc., means 1-6 carbon atoms,preferably 1-4 carbon atoms. X is a halogen atom. The radicals --COOR¹and --COOR⁸ are carboxylate functions; OR¹ and OR⁸ are alcohol residuesin which R¹ is a lower alkyl group and R⁸ is represented by the formula:##STR7## wherein, R⁹ is a hydrogen atom or a cyano group;

R¹⁰ is a hydrogen atom, a lower alkyl group, a phenoxy group, a benzylgroup or a phenylthio group;

R¹¹ is a hydrogen atom or a lower alkyl group; and

R¹² is a divalent oxygen or sulfur atom or a vinylene group, --CH═CH--.

R is either R¹ or R⁸.

Except as otherwise specified in the detailed descriptions for eachstep, the radicals R² -R⁷ appearing in the equations may be thefollowing:

Each of R² -R⁷ is a hydrogen atom, a lower alkyl group, a lower alkenylgroup, a lower alkynyl group, a lower cycloalkyl group, a phenyl group,an aralkyl group such as benzyl, a lower alkoxycarbonyl group, a loweralkanoyl group, an aroyl group such as benzoyl, a di(lower alkyl)amidegroup, a nitrile group or a lower haloalkyl group; the couples R² -R³,R⁴ -R⁵, and R⁶ -R⁷ may constitute lower alkylene chains of at least 2carbon atoms.

In the process of Step 1 an alkenol is reacted with an orthoester toproduce a γ-unsaturated carboxylate, Structure A. It has been found thatthe mixed orthoester, Structure W, is an intermediate and may beisolated. Other reactants capable of producing this intermediate, usefulin the practice of the process, could be employed to produce A; forexample, an alkenol may be reacted with an appropriate ketene acetal toproduce such a mixed orthoester from which the γ-unsaturatedcarboxylate, A, may be derived. The product of Step 1 is a lower alkylester which may optionally be reacted in Step 1' by ester interchangewith an alcohol, R⁸ OH, chosen from among alcohols which commonly appearin pyrethroids; for example, 3-phenoxybenzyl alcohol. The ester soproduced, Structure A', can be carried through the processes of Steps 2and 3 to yield, as the product of Step 3, adihalovinylcyclopropanecarboxylate which is a pyrethroid insecticide.

In the process of Step 2, the γ-unsaturated carboxylate, A or A', isthen treated with a carbon tetrahalide to produce a γ-halocarboxylate ofStructure B. The γ-halocarboxylate may be dehydrohalogenatedsubsequently with a base to produce any one of four different products,depending upon the choice of reaction conditions. The novelintermediates represented by Structures X, Y and Z, each representingthe elimination of 1 mole of HX from the γ-halocarboxylate, B, may, butneed not, be isolated. Each of the intermediates, X, Y and Z, is auseful composition of matter which can be carried to thedihalovinylcyclopropanecarboxylate, Structure C, by the elimination ofadditional HX. If the optional ester interchange of Step 1' was notcarried out on the γ-unsaturated carboxylate, A, thedihalovinylcyclopropanecarboxylate, C, may be treated by known processesto produce an active insecticide [Elliott, Nature, 244, 457 (1973)].

STEP 1

The first process of this invention is represented by Step 1 in which analkenol is reacted with an orthoester to produce a γ-unsaturatedcarboxylate, A, via the mixed orthoester, W, an intermediate which mayor may not be isolated. Examples of alkenols which may be employed inthe process of Step 1 are allyl alcohol, crotyl alcohol,4-methyl-1-phenyl-3-penten-2-ol, 4-methyl-3-penten-2-ol, cinnamylalcohol, 3-methyl-2-buten-1-ol, 2,4-dimethyl-3-penten-2-ol,5-methyl-4-hexen-3-ol, 2-methyl-2-hepten-4-ol,1-cyclopentyl-3-methyl-2-buten-1-ol and the like. The specific alkenolto be employed in Step 1 will depend upon the desired nature of R², R³,R⁴, and R⁵. These alkenols are readily available or are derived easilyfrom commercial raw materials. In order to produce a2-dihalovinylcyclopropanecarboxylate such as II or III, having dimethylsubstitution in position 3 of the cyclopropane ring,3-methyl-2-buten-1-ol is preferably employed. 3-Methyl-2-buten-1-ol isavailable as a by-product from the manufacture of isoprene.

Examples of orthoesters which may be employed in the process of Step 1include, in the acid part, alkanoic acids such as acetic acid, propionicacid, butyric acid, isobutyric acid and valeric acid; and in the alcoholpart, lower alkanols such as methanol and ethanol; e.g., ethylorthopropionate, methyl orthoacetate, ethyl orthoacetate, etc. The acidand alcohol portions of the orthoester will be chosen to yield thedesired R¹, R⁶, and R⁷ groups in the γ-unsaturated carboxylate. Theorthoesters may be prepared readily by the alcoholysis of thecorresponding nitriles. In producing a γ-unsaturated carboxylate whichis to be carried through the remaining processes of this invention toyield a dihalovinylcyclopropanecarboxylate, ethyl orthoacetate ispreferably employed.

Although the reaction between the alkenol and the orthoester does notrequire it, an acid catalyst increases the rate of the reaction.Examples of acid catalysts which may be employed include phenols such asphenol, ortho, meta or para-nitrophenol, ortho, meta or para-cresol,ortho, meta or para-xylenol, 2,6-dimethylphenol, 2,6-di-t-butylphenol,2,4,6-tri-sec-butylphenol, 2,4,6-tri-t-butylphenol,4-methyl-2,6-di-t-butylphenol, 4-methyl-3,5-di-t-butylphenol,hydroquinone, 2,5-di-t-butylhydroquinone, α or β-naphthol and the like;lower aliphatic acids such as acetic acid, propionic acid, butyric acid,isobutyric acid, cyclohexanecarboxylic acid, valeric acid and the like;aromatic carboxylic acids such as benzoic acid, meta-chlorobenzoic acidand the like; sulfonic acids such as benzenesulfonic acid,para-toluenesulfonic acid and the like; inorganic acids such ashydrochloric acid, sulfuric acid, phosphoric acid, boric acid and thelike; and Lewis acids such as zinc chloride, ferric chloride, mercuricacetate and the like. In order to avoid side reactions such asdehydration of the alkenol, phenols, aliphatic acids having 2 to 6carbon atoms and aromatic acids are preferred, with phenol being thecatalyst of choice in most instances.

The process of Step 1 does not require a solvent, but solvents which donot adversely affect the reaction or the product may be employed ifdesired. Useful solvents include decalin, n-octane, toluene, ortho, metaor para-xylene, di-n-butyl ether, N,N-dimethylformamide and the like.

Although the stoichiometry suggests that the alkenol and the orthoestershould be present in equimolar amounts, it is preferred that a slightexcess of the orthoester be employed. The acid catalyst can be used inan amount ranging from about 0.001 to 20% by weight, preferably from 1to 15% by weight, based on the amount of alkenol reacted.

The process of Step 1 can be conducted at temperatures ranging fromabout 20° to 250° C. It is preferred, however, to conduct the reactionin two stages, the first stage at a temperature ranging between 20° and120° C. and the second stage at a temperature between 100° and 250° C.If ethyl orthoacetate is employed as a reactant, and the reaction isconducted at atmospheric pressure, it is preferable to conduct the firststage at a temperature between about 100° and 120° C., removing ethanolby distillation as it is produced; the second stage is preferablyconducted at a temperature between about 140° and 170° C.

STEP 1'

The γ-unsaturated carboxylate, A, may, if desired, be reacted accordingto the process of Step 1' in which the alcohol residue, OR⁸, isinterchanged for the lower alkanol residue, OR¹, to produce theγ-unsaturated carboxylate, A', OR⁸ being chosen from among alcoholresidues which commonly appear in pyrethroids. The γ-unsaturatedcarboxylate, A', when carried through the processes of this inventionrepresented by Steps 2 and 3, may lead directly to adihalovinylcyclopropanecarboxylate, C, which is a pyrethroidinsecticide; e.g., Structure III.

The structure of the γ-unsaturated carboxylate, A, available for theprocess of Step 1' will depend upon the structures of the startingmaterials employed in Step 1.

For the purposes of the process of Step 1':

R² and R³ each is a hydrogen atom, a lower alkyl group, a lower alkenylgroup, a lower alkynyl group, a lower cycloalkyl group, a phenyl groupor an aralkyl group such as benzyl; R² and R³ together may constitute alower alkylene chain of at least 2 carbon atoms; and when one of R² andR³ is other than hydrogen, the other may be a lower alkoxycarbonylgroup, a lower alkanoyl group, an aroyl group such as benzoyl, a di(lower alkyl) amide group or a nitrile group.

R⁴ -R⁷ each is a hydrogen atom, a lower alkyl group, a lower alkenylgroup, a lower alkynyl group, a lower cycloalkyl group, a phenyl groupor an aralkyl group such as benzyl; the couples R⁴ -R⁵ and R⁶ -R⁷ mayconstitute lower alkylene chains of at least 2 carbon atoms.

The γ-unsaturated carboxylate and the alcohol may be employed inequimolar amounts, but it is preferable that one reactant be in excess.The ethyl ester is convenient to use, and when used, it is preferredthat sodium ethoxide be added as a catalyst and that ethanol be removedfrom the mixture as it is formed. A solvent such as toluene may beemployed.

Instead of introducing R⁸ in the manner just described, the interchangemay be conducted at another point in the process, and other syntheticmethods can be used for converting an R¹ ester to an R⁸ ester such ashydrolysis followed by esterification, for example, reaction of adihalovinylcyclopropanecarboxylic acid chloride with an alcohol R⁸ OH inthe presence of a base.

STEP 2

The process of this invention represented by Step 2 is a reactionbetween a γ-unsaturated carboxylate, A or A', and a carbon tetrahalide,CX₄, in the presence of a catalyst to produce a γ-halocarboxylate, B.The γ-unsaturated carboxylate, A or A', may be prepared as describedabove.

For the purposes of the process of Step 2:

R², R³, R⁶ and R⁷ each is a hydrogen atom, a lower alkyl group, a lowercycloalkyl group, a phenyl group, an aralkyl group such as benzyl, alower alkoxycarbonyl group, a lower alkanoyl group, an aroyl group suchas benzoyl, a di(lower alkyl)amide group, a nitrile group or a lowerhaloalkyl group; the couples R² -R³ and R⁶ -R⁷ may constitute loweralkylene chains of at least two carbon atoms.

R⁴ and R⁵ are hydrogen atoms.

Carbon tetrahalides which may be employed in this process include carbontetrachloride, carbon tetrabromide, bromotrichloromethane,bromochlorodifluoromethane and iodotrichloromethane. In general, thecarbon tetrahalide will contain no more than two fluorine atoms, and nomore than one iodine atom. When it is desired to produce adichlorovinylcyclopropanecarboxylate by the processes of this invention,carbon tetrachloride, bromotrichloromethane or dibromodichloromethanemay be employed; although bromotrichloromethane reacts smoothly, carbontetrachloride is more readily available and less expensive.

The process of Step 2 requires a catalyst, and two distinct types ofcatalyst systems have been found to be useful; (1) free radicalinitiators or (2) transition metal salts and coordination complexesbetween transition metal salts and various electron donors such asorganic amines, carbon monoxide, acetylacetone, etc. The reaction canalso be catalyzed by radiation; e.g., ultraviolet light, a variant ofthe reaction employing a free radical catalyst. In order for thereaction to be effectively catalyzed by visible light, the carbontetrahalide should preferably contain at least one bromine or iodineatom.

Examples of free radical catalysts which may be used includeazobisisobutyronitrile (AIBN), benzoyl peroxide (BPO), acetyl peroxide,di-t-butyl peroxide, t-butyl peracetate, t-butyl perbenzoate, t-butylperphthalate, t-butyl hydroperoxide and the like. The use of a catalyticamount of a free radical catalyst is generally sufficient, but amountsas high as 20% based on the number of moles of γ-unsaturated carboxylatemay be employed, especially if the catalyst is added in increments.

Examples of transition metal salts which can be used are cuprous orcupric chloride, ferrous or ferric chloride, cobalt, nickel, zinc,palladium, rhodium or ruthenium chloride, copper cyanide, copperthiocyanide, copper oxide, copper sulfide, copper or iron acetate, ironcitrate, iron sulfate, iron oxide, copper or iron acetylacetonate andthe like, including hydrates of the salts listed.

Examples of organic amines which can be used in conjunction with thetransition metal salts are aliphatic amines such as n-butylamine,diisopropylamine, triethylamine, cyclohexylamine, benzylamine,ethylenediamine, ethanolamine and the like; aromatic amines such asaniline, toluidine and the like; heterocyclic amines such as pyridineand the like; as well as amine salts such as diethylamine hydrochlorideand the like. With a view to the availability of materials and optimumyield, a combination of a transition metal halide and an aliphatic amineis preferred, especially ferric chloride hexahydrate and n-butylamine.In order to obtain the maximum yield of the desired product it has beenfound desirable to employ more than about 1.5 moles, preferably betweenabout 2 and 10 moles, of organic amine per mole of transition metalsalt. In general, the transition metal catalyst may be used in catalyticamounts, about 0.01% based on the number of moles of γ-unsaturatedcarboxylate, but higher concentrations increase the reaction rate, and10% or more may be used to advantage.

When a free radical catalyst is employed, it is preferable to useapproximately equimolar amounts of the starting materials in the absenceof a solvent. However, if desired, solvents which do not adverselyaffect the reaction; for example, carbon disulfide or hydrocarbonsolvents such as benzene or toluene may be used. The reaction may alsobe conducted in the presence of an excess amount of the carbontetrahalide as a solvent; the excess can be recovered and recycled. Thereaction is preferably conducted at a molar ratio of carbon tetrahalideto γ-unsaturated carboxylate between about 1:1 and 4:1.

When catalyzed by light, the reaction may be conducted at temperaturesbetween about 25° and 100° C. When free radical catalysts are used, thereaction is generally conducted at a temperature between about 50° and150° C.

When a transition metal salt or a coordination complex is used as thecatalyst, the reactants may be in approximately equimolar amounts, butthe carbon tetrahalide may also be employed in excess. A solvent is notnecessarily required in the reaction, but solvents which do notadversely affect the reaction or the product may be employed if desired;for example acetonitrile, dimethylformamide, alcohols, aliphatichydrocarbons, aromatic hydrocarbons, etc., may be used. Alternatively,the carbon tetrahalide may be used as the solvent as well as a reactant,if the carbon tetrahalide is a liquid. When a solvent is used, a polarsolvent is preferred since the yield generally is increased thereby. Acoordination complex of a metal salt with an electron donor is usuallypreferred to the salt itself, butylamine being a useful donor, withferric chloride hexahydrate a preferred salt. When a metal salt orcoordination complex is employed as the catalyst, the reaction isgenerally conducted in the temperature range 50° to 200° C., preferablybetween about 70° and 150° C.

The coordination complex catalysts retain their activity over a longperiod of time, and, in addition, can be reusued. For these reasons,they are preferred over most free radical catalysts.

STEP 3

The process of this invention represented by Step 3 involves thebase-induced dehydrohalogenation of the γ-halocarboxylate, B, to producea dihalovinylcyclopropanecarboxylate, C, via the intermediates X, Y orZ, compositions of matter which are useful in the practice of theprocess, which may or may not be isolated depending upon the reactionconditions. In the conversion of B to C, 2 moles of acid, HX, areeliminated and the elimination can be made to take place one mole at atime.

The structure of the γ-halocarboxylate, B, will be dictated by thestructures of the materials employed in Steps 1, 1' and 2.

For the purposes of the process of Step 3:

R² and R³ each is a hydrogen atom, a lower alkyl group, a lower alkenylgroup, a lower alkynyl group, a lower cycloalkyl group, a phenyl groupor an aralkyl group such as benzyl; R² and R³ together may constitute alower alkylene chain of at least 2 carbon atoms; and when one of R² andR³ is other than hydrogen, the other may be a lower alkoxycarbonylgroup, a lower alkanoyl group, an aroyl group such as benzoyl, adi(lower alkyl)amide group, or a nitrile group.

R⁴, R⁵ and R⁶ are hydrogen atoms.

R⁷ is a hydrogen atom, a lower alkyl group, a lower alkenyl group, alower alkynyl group, a lower cycloalkyl group, a phenyl group, anaralkyl group such as benzyl, a lower alkoxycarbonyl group, a loweralkanoyl group, an aroyl group such as benzoyl, a di(lower alkyl)amidegroup or a nitrile group.

When it is desired to produce a dihalovinylcyclopropanecarboxylate whichmay be converted readily into pyrethroid insecticides of the typerepresented by II and III, the γ-halocarboxylate will be chosen suchthat R⁴, R⁵, R⁶ and R⁷ are hydrogen; R² and R³ are methyl groups and Xis chlorine. Among compounds of that type, it has been found that anespecially useful and preferred one is the novel compound, ethyl3,3-dimethyl-4,6,6,6-tetrachlorohexanoate.

The nature and quantity of the base which is used, the solvents, and thetemperature determine whether the product of the reaction will be one ofthe intermediates X, Y or Z, or whether the reaction will proceed allthe way to the dihalovinylcyclopropanecarboxylate, C.

If it is desired to produce the dihalovinylcyclopropanecarboxylate, C,directly, anhydrous bases which can be used in the process of Step 3include sodium hydroxide and potassium hydroxide; alkali metal alkoxidessuch as sodium ethoxide, sodium methoxide, sodium t-butoxide, potassiumt-butoxide, and the like, previously prepared or prepared in situ;sodium hydride, sodium naphthalene and the like; but the use of sodiumhydride or an alkali metal alkoxide is preferred. At least 1.5 molarequivalents of the base, preferably 2 to 5 molar equivalents per mole ofγ-halocarboxylate should be used. The process can be carried outadvantageously in a solvent. Examples of solvents which can be used arealcohols, such as methanol, ethanol, t-butanol, etc., as well as etherssuch as diethyl ether, tetrahydrofuran, dimethoxyethane and the like.

It was found that the ratio of cis to trans isomers in the final productcan be varied over an unexpected range by simply changing thetemperature employed. For example, when the base-solvent combination issodium t-butoxide in tetrahydrofuran, and the reaction is conducted atabout 0°, the cis: trans ratio is about 50:50; whereas when the reactionis carried out near room temperature from intermediate Y, the cis: transratio is approximately 10:90.

To produce directly the dihalovinylcyclopropanecarboxylate, C, from B,the reaction generally may be conducted in the temperature range 50° to200° C., preferably 60° to 100° C.; but if sodium or potassiumt-butoxide and an ethereal solvent such as tetrahydrofuran are utilized,the reaction may be carried out at temperatures as low as -30° C.

To conduct the process of Step 3 so as to stop at intermediate X, thereaction should be conducted at a temperature no higher than about 25°C. in order to avoid the formation of Y, which is produced via X, and itis preferred that the γ-halogen atom in B have a high atomic number,such as bromine or iodine. In general, the use of an aprotic solventfavors the formation of X, and diethyl ether, tetrahydrofuran,dimethylformamide, dimethyl sulfoxide and the like may be employed. Anyof the bases specified above to produce thedihalovinylcyclopropanecarboxylate, C, may be used, but the sodium orpotassium lower alkoxides, especially ethoxides are preferred.Generally, between 1 and 2 moles of base per mole of γ-halocarboxylateare employed, but about 1.2 moles of base per mole of γ-halocarboxylateis preferred.

To conduct the process of Step 3 such that the intermediate Y isproduced from the γ-halocarboxylate, B, a polar aprotic solvent andhigher temperatures may generally be employed; an effective combinationis sodium ethoxide in dimethylformamide between the temperatures ofabout 25° and 150° C., with 50° to 150° C. being preferred. IntermediateY may also be made from intermediate X by heating the latter or byemploying an acid in catalytic amounts. The heat-induced isomerizationcan be carried out at temperatures between about 50° and 200° C. Attemperatures below about 50° C. the reaction proceeds slowly, whileabove 200° C. undesired by-products are formed. The preferredtemperature range is 100° to 170° C. Examples of acid catalysts whichcan be used to effect the isomerization are aliphatic acids such asacetic acid, propionic acid, butyric acid, isobutyric acid and the like;phenols such as phenol, hydroquinone and the like; and Lewis acids suchas aluminum chloride, zinc chloride and the like. Protonic acids aregenerally preferred to Lewis acids since they give higher yields. Theacid catalyst is generally employed in amounts ranging from about 0.05to 10 mole percent of catalyst per mole of X. It is anticipated that thecombination of an acid catalyst with thermal treatment will increase therate of isomerization. It is not necessary that the isomerization beconducted in the presence of a solvent, but, if desired, solvents whichdo not adversely affect the reaction or the product may be employed; forexample, benzene, toluene, xylene, tetralin, petroleum ether,dimethoxyethane, di(methoxyethyl)ether and the like.

The process of Step 3 may also be utilized to prepare the intermediate Zfrom the γ-halocarboxylate, B. In that case, the base may be eithersodium or potassium t-butoxide, preferably in excess with respect to theγ-halocarboxylate. Solvents such as benzene, dioxane, dimethylformamideor tetrahydrofuran may be utilized. t-Butyl alcohol may be used and amixture with benzene is preferred. The reaction may be carried outsuccessfully at temperatures ranging from about 25° to 50° C.

In any case in which it is desired to produce thedihalovinylcyclopropanecarboxylate, C, from any of the intermediates X,Y or Z, the conditions described above for making C from theγ-halocarboxylate, B, may be employed.

A wide variety of cyclopropanecarboxylates closely related to thedihalovinylcyclopropanecarboxylates may be prepared by the processes ofthis invention. For example, in Step 2, in place of a carbontetrahalide, other structurally similar polyhalogenated compounds,including chloroform, bromoform, α,α,α-trihalotoluene, lowertrihaloacetates, trihaloacetonitriles, and polyhalogenated loweralkanes, may be added to the olefinic double bond. Such additions willgive products analogous to the γ-halocarboxylates described above, butwith a substituent other than halogen in the ε-position, a substituentsuch as hydrogen, lower alkyl, lower haloalkyl, phenyl, nitrile, orlower alkoxycarbonyl. These products will undergo dehydrohalogenationand ring closure to form cyclopropanecarboxylates useful as insecticidesor in the preparation of insecticides. Similarly, intermediates of typesX and Y may be prepared with the above-noted substituents other thanhalogen in the ε-position, and these compounds may also be used toprepare β-substituted vinylcyclopropanecarboxylates where aβ-substituent is other than halogen. For example, ethyl4,6-dichloro-3,3-dimethyl-5-hexenoate is reacted with sodium t-butoxidein benzene to form ethyl2-(β-chlorovinyl)-3,3-dimethylcyclopropanecarboxylate.

Other means of introducing halogen may also be used to prepare compoundscapable of undergoing the dehydrohalogenation and ring closure of Step3. γ-Unsaturated alkenoates may be halogenated in the ε-position with ahalogenating agent, for example N-bromosuccinimide (NBS), to formcompounds analogous to the X intermediates described above. Suchcompounds will also undergo dehydrohalogenation and ring closure to formcyclopropanecarboxylates. The reaction sequence is illustrated below:##STR8## where R¹, R², R³, R⁷ and X are as previously defined for Step2, except neither R² nor R³ is hydrogen; R¹³ and R¹⁴ are hydrogen, loweralkyl, or phenyl.

The practice of this invention is illustrated further by the additionalexamples which follow.

EXAMPLE III Synthesis of Ethyl2-(β,β-Dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate A. Preparationof ethyl 3,3-dimethyl-4-pentenoate

A mixture of 12.9 g (0.15 mole) of 3-methyl-2-buten-1-ol, 48.6 g (0.3mole) of ethyl orthoacetate and 0.5 g of hydroquinone was heated at 140°for 20 hours with stirring. Ethanol was removed by distillation duringthe heating. At the end of 20 hours, the mixture was distilled underreduced pressure to give, after removal of unreacted ethyl orthoacetate,17.6 g (75% yield) of ethyl 3,3-dimethyl-4-pentenoate, b.p. 74°-78°/55mm.

B. Addition of bromotrichloromethane to ethyl 3,3-dimethyl-4-pentenoate

Fifty milligrams of azobisisobutyronitrile was added to a solution of1.56 g (0.01 mole) of ethyl 3,3-dimethyl-4-pentenoate in 5 ml ofbromotrichloromethane. The mixture was heated for 10 hours at 130°.Unreacted bromotrichloromethane was removed, and the residue wasdistilled under reduced pressure to give 3.2 g (89% yield) of ethyl4-bromo-6,6,6-trichloro-3,3-dimethylhexanoate, b.p. 102°-105°/0.1 mm.

Calculated for C₁₀ H₁₆ BrCl₃ O₂ : C, 33.88; H, 4.55; Found: C, 33.83; H,4.35.

nmrδppm (CCl₄): 4.49 (q, 1H), 4.08 (q, 2H), 3.29 (s, 1H), 3.32 (d, 1H),2.42 (q, 2H), 1.35-1.13 (m, 9H).

C. Simultaneous cyclization and dehydrochlorination

A solution of 709 mg (2 mmoles) of ethyl4-bromo-6,6,6-trichloro-3,3-dimethylhexanoate in 5 ml of anhydroustetrahydrofuran was added dropwise to a suspension of 448 mg (4 mmoles)of potassium t-butoxide in 15 ml of tetrahydrofuran and the mixture washeated under reflux for 2 hours. The mixture was then allowed to cooland an additional 220 mg of potassium t-butoxide was added. The mixturewas heated under reflux for 1 hour. Then, another 110 mg of potassiumt-butoxide was added, and the mixture again was heated under reflux for1 hour. The mixture was poured into ice water and extracted with diethylether. The ether extract was dried over magnesium sulfate, the ether wasremoved by distillation, and the residue was distilled under reducedpressure to give 330 mg (70% yield) of ethyl2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate, b.p. 86°/0.5mm.

Analysis: nmrδppm (CCl₄): 6.22 (d,0.5H), 5.56 (d,0.5H), 4.05 (b.q., 2H),2.35-1.05 (m, 11H).

ir (cm⁻¹): 3060, 1730, 1615, 1230, 1182, 1145, 1120, 1087, 925, 860,817, 790, 765, 702, 650.

EXAMPLE IV Synthesis of Ethyl2-(β,β-Dibromovinyl)-3,3-dimethylcyclopropanecarboxylate A. Addition ofcarbon tetrabromide to ethyl 3,3-dimethyl-4-pentenoate

Fifty milligrams of azobisisobutyronitrile was added to a mixture of1.56 g (0.01 mole) of ethyl 3,3-dimethyl-4-pentenoate and 3.32 g (0.01mole) of carbon tetrabromide. The mixture was heated for 5 hours at 120°under an argon atmosphere. The mixture was then allowed to cool and waspurified by column chromatography with a silica gel column and a 1:1mixture of benzene and hexane as the eluting solvent. Concentration ofthe eluant gave 3 g (60% yield) of ethyl4,6,6,6-tetrabromo-3,3-dimethylhexanoate.

Analysis: Calculated for C₁₀ H₁₆ Br₄ O₂ : C,24.62; H,3.31; Br,65.51;Found: C,24.87; H,3.25; Br,65.60.

nmrδppm (CCl₄): 4.35 (q, 1H), 4.07 (q, 2H), 3.55 (m, 2H), 2.43 (q, 2H),1.40-1.15 (m, 9H).

B. Simultaneous cyclization and dehydrobromination

To 1.46 g of ethyl 4,6,6,6-tetrabromo-3,3-dimethylhexanoate in 16 ml ofabsolute ethanol was added dropwise 5 ml of an ethanol solutioncontaining 0.62 g of sodium ethoxide. The mixture was cooled in icethroughout the addition. The mixture was warmed to room temperature andstirred for 6 hours. An additional 2.5 ml of ethanolic sodium ethoxide(about 0.3 g) was added, and the mixture was stirred for an additional12 hours. The mixture was then poured into ice water and extracted withdiethyl ether. The ether solution was dried over magnesium sulfate anddistilled to give 0.77 g (79% yield) of ethyl2-(β,β-dibromovinyl)-3,3-dimethylcyclopropanecarboxylate, b.p.98°-101°/0.4 mm.

Analysis: Calculated for C₁₀ H₁₄ Br₂ O₂ : C,36.84; H,4.33; Br,49.02;Found: C,37.07; H,4.40; Br,49.27.

nmrδppm (CCl₄): 6.12 (d, 1H), 4.08 (q, 2H), 2.20-1.40 (m, 2H), 1.37-1.10(m, 9H).

ir (cm⁻¹): 1725, 1223, 1175, 855, 800, 762.

EXAMPLE V Synthesis of Ethyl 3,3-Dimethyl-4-pentenoate A. Using phenolas catalyst

A mixture of 43 g (0.5 mole) of 3-methyl-2-buten-1-ol, 97 g (0.6 mole)of ethyl orthoacetate, and 7.0 g (0.075 mole) of phenol was heated at135°-140° with stirring for 9-10 hours. Ethanol was distilled from themixture as the reaction proceeded. When the evolution of ethanol hadceased, heating was discontinued and the mixture was allowed to cool toroom temperature. The mixture was then dissolved in diethyl ether andthe ethereal solution was treated with IN hydrochloric acid to decomposeunreacted ethyl orthoacetate. The ethereal solution was then washedsuccessively with a saturated aqueous solution of sodium bicarbonate andwith water, then dried over magnesium sulfate. The dried solution wasconcentrated and distilled under reduced pressure to give 60.8 g (78%yield) of ethyl 3,3-dimethyl-4-pentenoate, b.p. 57°-60°/11 mm.

Analysis: nmr δ ppm (CCl₄): 6.15-5.60 (d.d. 1H), 5.15-4.68 (m, 2H), 4.02(q, 2H), 2.19 (s, 2H), 1.45-1.05 (m, 9H).

ir (cm⁻¹): 3090, 1740, 1640, 1370, 1240, 1120, 1030, 995, 910.

B. Using boric acid as catalyst

A mixture of 4.3 g of 3-methyl-2-buten-1-ol, 16.2 g of ethylorthoacetate and 86 mg of boric acid was heated for 2 hours at 120° withstirring, during which ethanol was evolved and removed. The temperaturewas then increased to 145°-150° where it was maintained for anadditional 8 hours. When ethanol evolution ceased, the mixture wasdistilled to separate unreacted ethyl orthoacetate from 6.25 g (80%yield) of ethyl 3,3-dimethyl-4-pentenoate, b.p. 78°-80°/51 mm.

C. Using phosphoric acid as catalyst

A mixture of 4.3 g of 3-methyl-2-buten-1-ol, 16.2 g of ethylorthoacetate and 3 drops of phosphoric acid was reacted as described inExample V A to give 6.15 g (79% yield) of ethyl3,3-dimethyl-4-pentenoate, b.p. 87°-88°/58 mm.

D. Using isobutyric acid as catalyst

A mixture of 0.65 g of 3-methyl-2-buten-1-ol, 2.43 g of ethylorthoacetate and 50 mg of isobutyric acid was treated as described inExample I A. Gas chromatographic analysis of the benzene solution showedthat ethyl 3,3-dimethyl-4-pentenoate had been produced in 70% yield.

E. Using mercuric acetate as catalyst

Example I A was repeated, substituting 50 mg of mercuric acetate for thephenol, giving ethyl 3,3-dimethyl-4-pentenoate in 69% yield (based ongas chromatographic analysis).

F. Using hydroquinone as catalyst

Example I A was repeated, substituting 25 mg of hydroquinone for thephenol, giving ethyl 3,3-dimethyl-4-pentenoate in 51% yield (based ongas chromatographic analysis).

G. Without catalyst

A mixture of 4.3 g of 3-methyl-2-buten-1-ol and 8.1 g of ethylorthoacetate was heated with stirring. The temperature was increasedslowly from room temperature to 165° over 2 hours, during which 2.21 gof ethanol was collected. The temperature was maintained at 165° for 26hours, during which time an additional 1.52 g of ethanol was collected.The reaction mixture was then allowed to cool and diluted with diethylether. The ether solution was washed successively with dilutehydrochloric acid, saturated aqueous sodium bicarbonate and saturatedaqueous sodium chloride. The washed solution was dried over magnesiumsulfate and distilled to give 4.03 g (52% yield) of ethyl3,3-dimethyl-4-pentenoate, b.p. 80°-85°/52 mm.

H. Via 1,1-diethoxy-1-(3-methyl-2-buten-1-yloxy)ethane (an IntermediateW)

1. Preparation of 1,1-diethoxy-1-(3-methyl-2-buten-1-yloxy)ethane

A mixture of 4.3 g of 3-methyl-2-buten-1-ol and 16.2 g of ethylorthoacetate was heated with stirring. The temperature was raised slowlyover 2 hours to 120°, during which time 1.8 g of ethanol was evolved andremoved. Heating was continued at 120° for 30 minutes and the reactionmixture was then distilled to give, after removal of 8.5 g of unreactedethyl orthoacetate (b.p. 50°-65°/57 mm), 4.25 g of1,1-diethoxy-1-(3-methyl-2-buten-1-yloxy)ethane, b.p. 75°-76°/6 mm.

Analysis: Calculated for C₁₁ H₂₂ O₃ : C, 65.31; H, 10.96; Found: C,65.52; H, 10.74.

2. Preparation of ethyl 3,3-dimethyl-4-pentenoate

A mixture of 2.02 g of 1,1-diethoxy-1-(3-methyl-2-buten-1-yloxy)ethaneand 20 mg of phenol was heated for 12 hours at 150°-160°, during whichtime ethanol was evolved. Distillation of the residue gave 1.12 g (72%yield) of ethyl 3,3-dimethyl-4-pentenoate, b.p. 80°-83°/57 mm.

Similarly, in the absence of phenol, 2.02 g of1,1-diethoxy-1-(3-methyl-2-buten-1-yloxy)ethane was heated for 20 hoursat 150°-160°. Distillation then gave 1.06 g (68% yield) of ethyl3,3-dimethyl-4-pentenoate, b.p. 87°-89°/62 mm.

EXAMPLE VI Synthesis of Other γ-Unsaturated Carboxylates A. Ethyl2,3,3-trimethyl-4-pentenoate

A mixture of 3.44 g (0.04 mole) of 3-methyl-2-buten-1-ol, 14.08 g (0.08mole) of ethyl orthopropionate and 0.35 g of phenol was heated at 140°with stirring for 24 hours, the evolved ethanol being collected. Thereaction mixture was then distilled to give, after removal of unreactedethyl orthopropionate, 4.76 g (70% yield) of ethyl2,3,3-trimethyl-4-pentenoate, b.p. 90°-92°/45 mm.

Analysis: nmr δ ppm (CCl₄): 6.10-5.55 (d.d. 1H), 5.10-4.70 (m, 2H), 4.05(q, 2H), 2.25 (q, 1H), 1.22 (t, 3H), 1.20-0.95 (m, 9H).

B. Ethyl 2-methyl-3-phenyl-4-pentenoate

A mixture of 2.68 g of cinnamyl alcohol, 7.04 g of ethyl orthopropionateand 300 mg of phenol was treated as described in Example VI A to give,on distillation, 2.07 g (62% yield) of ethyl2-methyl-3-phenyl-4-pentenoate, b.p. 104°/1.5 mm.

Analysis: nmr δ ppm (CCl₄): 7.12 (b.s., 5H), 6.30-4.80 (m, 3H),4.26-3.20 (m, 3H), 3.00-2.50 (m, 1H), 1.40-0.78 (m, 6H).

C. Ethyl 2,3-dimethyl-4-pentenoate

A mixture of 1.44 g of 2-buten-1-ol, 7.04 g of ethyl orthopropionate and30 mg of boric acid was heated at 120° with stirring for 2 hours. Thetemperature was then increased to 140° where it was maintained for 20hours. Distillation gave a mixture of unreacted orthopropionate and thedesired product. The distillate was dissolved in diethyl ether. Theethereal solution was washed three times with 1N hydrochloric acid, thensuccessively with saturated aqueous sodium bicarbonate and sodiumchloride. The washed ethereal solution was dried over magnesium sulfateand distilled to give 1.64 g (53% yield) of ethyl2,3-dimethyl-4-pentenoate, b.p. 90°-92°/65 mm.

Analysis: nmr δ ppm (CCl₄): 5.85-5.37 (m, 1H), 5.04-4.78 (m, 2H), 4.02(q, 2H), 2.56-1.98 (m, 2H), 1.22 (t, 3H), 1.20-0.88 (m, 6H).

D. Methyl 2-ethyl-3,3-dimethyl-4-pentenoate

A mixture of 10.32 g of 3-methyl-2-buten-1-ol, 26.6 g of methylorthobutyrate and 200 mg of phenol was heated at 120° with stirring for2 hours. The temperature was then increased to 140° where it wasmaintained for 23 hours. The mixture was distilled to give, afterremoval of unreacted ethyl orthobutyrate, 11.55 g (57% yield) of methyl2-ethyl-3,3-dimethyl-4-pentenoate, b.p. 91°-94°/45 mm.

Analysis: nmr δ ppm (CCl₄): 5.78 (d.d. 1H), 5.13-4.70 (m, 2H), 3.61 (s,3H), 2.32-1.98 (m, 1H), 1.90-1.20 (m, 2H), 1.02 (s, 6H), 0.80 (b.t.,3H).

In the same manner the following γ-unsaturated carboxylates wereprepared:

E. Ethyl 3-phenyl-4-pentenoate, b.p. 76°-77°/0.2 mm.

F. Ethyl 3-methyl-4-pentenoate, b.p. 85°-89°/63 mm.

G. Ethyl 2,3,3-trimethyl-4-hexenoate, b.p. 97°-99°/37 mm.

H. Ethyl 2,3,3,5-tetramethyl-4-hexenoate, b.p. 115°-117°/40 mm.

I. Ethyl 2,3,3-trimethyl-4-heptenoate, b.p. 120°-122°/45 mm.

J. Ethyl 2,3,3-trimethyl-4-octenoate, b.p. 128°-131°/40 mm.

K. Methyl 2-ethyl-3,3-dimethyl-4-hexenoate, b.p. 97°-100°/30 mm.

L. Ethyl 3,3-dimethyl-4-hexenoate, b.p. 103°-105°/57 mm.

M. Ethyl 3,3-dimethyl-4-heptenoate, b.p. 103°-107°/38 mm.

N. Ethyl 3,3-dimethyl-4-octenoate, b.p. 114°-116°/33 mm.

O. Ethyl 3,3,5-trimethyl-4-hexenoate, b.p. 100°-104°/45 mm.

P. Ethyl 5-cyclopentyl-3,3-dimethyl-4-pentenoate, b.p. 119°-123°/15 mm.

Q. Ethyl 3,3,6-trimethyl-4-heptenoate, b.p. 90°-93°/30 mm.

R. Ethyl 3,3,5-trimethyl-4-heptenoate, b.p. 100°-104°/20 mm.

S. Benzyl 3,3-dimethyl-4-pentenoate

In the manner of Example I B, 810 mg of benzyl alcohol was reacted with1122 mg of ethyl 3,3-dimethyl-4-pentenoate in the presence of 48 mg ofsodium ethoxide in 30 ml of toluene to give 1.0 g (65% yield) of benzyl3,3-dimethyl-4-pentenoate, b.p. 92°-98°/0.1 mm.

Analysis: Calculated for C₁₄ H₁₈ O₂ : C, 76.49; H, 8.51; Found: C,76.79; H, 8.25.

nmr δ ppm (CCl₄): 7.29 (b.s., 5H), 5.84 (d.d., 1H), 5.03 (s, 2H),5.05-4.70 (m, 2H), 2.22 (s, 2H), 1.06 (s, 6H).

T. Using similar techniques, the following γ-unsaturated carboxylatescan be prepared:

1. isopropyl 2-benzyl-3,3-dimethyl-4-pentenoate

2. t-butyl 3,3-dimethyl-4-pentenoate

3. ethyl 2-cyclopentyl-4-pentenoate

4. ethyl 3-ethyl-3-methyl-4-pentenoate

5. ethyl 3-ethyl-3-isopropyl-4-pentenoate

6. ethyl 3-t-butyl-3-propyl-4-pentenoate

7. ethyl 3-methyl-3-vinyl-4-pentenoate

8. ethyl 3-(2-butenyl)-3-ethyl-4-pentenoate

9. ethyl 2-(1-vinylcyclohexyl)acetate

10. ethyl 3-(2-butynyl)-3-methyl-4-pentenoate

11. ethyl 3-cyclohexyl-3-methyl-4-pentenoate

12. ethyl 3-benzyl-3-methyl-4-pentenoate

13. ethyl 2-benzoyl-3-carbethoxy-4-pentenoate

14. ethyl 3-acetyl-4-pentenoate

15. ethyl 3-benzoyl-4-pentenoate

16. ethyl 3-(N,N-dimethylcarboxamido)-4-pentenoate

17. ethyl 3-(N-ethyl-N-isopropylcarboxamido)-4-pentenoate

18. ethyl 3-cyano-2-ethynyl-4-pentenoate

19. ethyl 3-chloromethyl-4-pentenoate

20. ethyl 3-(2-bromoethyl)-4-pentenoate

21. ethyl 3-(1-fluoro-1-methylethyl)-4-pentenoate

22. ethyl 3,3-diphenyl-4-pentenoate

23. ethyl 5-allyl-3,3-dimethyl-4-hexenoate

24. ethyl 3,3-dimethyl-5-phenyl-4-pentenoate

25. methyl 5-cyclohexyl-4-pentenoate

26. ethyl 4-cyclohexylidene-3,3-dimethylbutanoate

27. ethyl 5-carbomethoxy-3,3-dimethyl-4-pentenoate

28. ethyl 5-(2-butynyl)-3,3-dimethyl-4-pentenoate

29. ethyl 5-acetyl-3,3-dimethyl-4-pentenoate

30. ethyl 5-benzyl-3,3-dimethyl-4-pentenoate

31. ethyl 3,3-dimethyl-5-(N,N-dimethylcarboxamido)-4-pentenoate

32. ethyl 5-cyano-3,3-dimethyl-4-pentenoate

33. ethyl 5-benzoyl-3,3-dimethyl-4-pentenoate

34. ethyl 5-(2-bromoethyl)-3,3-dimethyl-4-pentenoate

35. ethyl 2,2,3,3-tetramethyl-4-pentenoate

36. ethyl 2,3,3-trimethyl-2-isopropyl-4-pentenoate

37. ethyl 2-chloromethyl-2-phenyl-4-pentenoate

38. ethyl 3,3-dimethyl-2,2-diphenyl-4-pentenoate

39. ethyl 2-carbomethoxy-3,3-dimethyl-4-pentenoate

40. ethyl 2-acetyl-3,3-dimethyl-4-pentenoate

41. ethyl 2-butyryl-3,3-dimethyl-4-pentenoate

42. ethyl 3,3-dimethyl-2-(N,N-dimethylcarboxamido)-4-pentenoate

43. ethyl 2-cyano-3,3-dimethyl-4-pentenoate

44. ethyl 1-allyl-1-cyclohexanecarboxylate

45. methyl 2-cyano-3-ethyl-4-heptenoate

46. isopropyl 5-chloromethyl-2-vinyl-4-pentenoate

47. methyl3-cyano-2-(N,N-dimethylcarboxamido)-5-(2-fluoroethyl)-4-hexenoate

EXAMPLE VII Synthesis of Ethyl 4,6,6,6-Tetrahalo-3,3-dimethylhexanoatesby Addition of Carbon Tetrahalides to Ethyl 3,3-Dimethyl-4-pentenoate A.Addition of carbon tetrachloride in the presence of ferric chloride,butylamine and acetonitrile

Example II A was repeated except that the dimethylformamide was replacedby 1.23 g of acetonitrile, producing 2.54 g (82% yield) of ethyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate.

B. Addition of carbon tetrachloride in the presence of ferric chlorideand butylamine without added solvent

Example II A was repeated, omitting the dimethylformamide, to give 2.23g (72% yield) of ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate.

C. Addition of carbon tetrabromide in the presence of ferric chloride,butylamine and dimethylformamide

A mixture of 135.2 mg (0.5 mmole) of ferric chloride hexahydrate, 146.3mg (2.0 mmoles) of n-butylamine, 2.19 g of dimethylformamide, 1.56 g (10mmoles) of ethyl 3,3-dimethyl-4-pentenoate, and 3.32 g (10 mmoles) ofcarbon tetrabromide in a sealed tube was heated for 20 hours at 120°.The tube was allowed to cool and the contents were diluted withchloroform. The chloroform solution was washed successively with 1Nhydrochloric acid, saturated aqueous sodium bicarbonate and water. Thewashed chloroform solution was dried over magnesium sulfate anddistilled to give 2.9 g (60% yield) of ethyl4,6,6,6-tetrabromo-3,3-dimethylhexanoate, b.p. 144°/0.2 mm.

D. Addition of bromotrichloromethane in the presence of ferric chloride,butylamine and dimethylformamide

Example VII C was repeated using 2.0 g (10 mmoles) ofbromotrichloromethane instead of carbon tetrabromide to obtain 3.1 g(70% yield) of ethyl 4-bromo-6,6,6-trichloro-3,3-dimethylhexanoate, b.p.128°/0.25 mm.

E. Addition of carbon tetrachloride in the presence of ferric chloride,butylamine and dimethylformamide

A mixture of 94.5 mg (0.35 mmole) of ferric chloride hexahydrate, 102 mg(1.4 mmole) of butylamine, 1.2 ml of dimethylformamide, 780 mg (5mmoles) of ethyl 3,3-dimethyl-4-pentenoate, and 1.54 g (10 mmoles) ofcarbon tetrachloride in a sealed tube was heated for 15 hours at 120°.The contents of the tube were cooled to room temperature and dilutedwith carbon tetrachloride to a final volume of 5 ml. Gas chromatographicanalysis of the solution showed that ethyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate had been produced in 95%yield.

F. Addition of carbon tetrachloride in the presence of ferrous chloride,butylamine and dimethylformamide

Example VII E was repeated using 74.7 mg (0.25 mmole) of ferrouschloride instead of ferric chloride. Gas chromatographic analysis showedan 82% yield of ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate.

Example VII E was repeated using the following catalysts instead offerric chloride to produce ethyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate in the stated yields:

G. Cuprous chloride

76% yield.

H. Cupric cyanide

72% yield.

I. Ethanol as solvent

Repetition of Example VII E using 690 mg of absolute ethanol instead ofthe dimethylformamide resulted in an 80% yield of ethyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate.

J. Addition of carbon tetrachloride in the presence of benzoyl peroxide

A mixture of 3.12 g (0.02 mole) of ethyl 3,3-dimethyl-4-pentenoate, 30ml of carbon tetrachloride, and 50 mg of benzoyl peroxide in a pressurevessel was heated for 4 hours at 140°. The vessel was cooled, anadditional 50 mg of benzoyl peroxide was added and the vessel was againheated at 140° for 4 hours. After cooling to room temperature, themixture was washed successively with saturated aqueous sodiumbicarbonate and water. The mixture was dried over magnesium sulfate anddistilled to give 4.56 g (74% yield) of ethyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate, b.p. 107°-108°/0.3 mm.

K. Photocatalyzed addition of carbon tetrabromide

A mixture of ethyl 3,3-dimethyl-4-pentenoate (0.78 g) and carbontetrabromide (3.32 g), continuously purged with argon, was irradiatedwith a 200 watt visible light source for 10 hours at room temperature.The resulting dark-brown oil was purified by column chromatography toafford 1.46 g (59.8% yield) of ethyl4,6,6,6-tetrabromo-3,3-dimethylhexanoate.

EXAMPLE VIII Addition of Carbon Tetrahalides to Other γ-UnsaturatedCarboxylates A. Ethyl 4,6,6,6-tetrachloro-2,3,3-trimethylhexanoate

1. Using benzoyl peroxide

A mixture of 1.36 g (8 mmoles) of ethyl 2,3,3-trimethyl-4-pentenoate, 20ml of carbon tetrachloride, and 50 mg of benzoyl peroxide was chargedinto a pressure vessel. The vessel was purged with argon, sealed andheated for 5 hours at 130°-140°. At 5-hour intervals thereafter, thevessel was cooled, an additional 50 mg of benzoyl peroxide was added,the reactor was repurged, resealed, and heating was continued until atotal of 200 mg of benzoyl peroxide had been added and 20 hours heatingtime had elapsed. The mixture was allowed to cool, then was washedsuccessively with saturated aqueous sodium bicarbonate and saturatedaqueous sodium chloride, then dried over magnesium sulfate. Distillationgave 1.81 g (70% yield) of ethyl4,6,6,6-tetrachloro-2,3,3-trimethylhexanoate, b.p. 106°-107°/0.3 mm.

Analysis: nmr δ ppm (CCl₄): 4.43-3.85 (m, 3H), 3.45-3.00 (m, 2H),2.97-2.63 (m, 1H), 1.35-0.95 (m, 12H).

2. Using ferric chloride, butylamine and dimethylformamide

A mixture of 1.7 g of ethyl 2,3,3-trimethyl-4-pentenoate, 3.08 g ofcarbon tetrachloride, 190 mg of ferric chloride hexahydrate, 205 mg ofn-butylamine, and 2.2 g of dimethylformamide was charged into a pressurevessel. The vessel was purged with argon, sealed and heated for 10 hoursin a bath maintained at 120°. The vessel was allowed to cool to roomtemperature, and the contents were diluted with diethyl ether. The ethersolution was washed successively with water, 1N hydrochloric acid,saturated aqueous sodium bicarbonate and water, then dried overmagnesium sulfate. The dried solution was distilled to give 1.6 g (49%yield) of ethyl 4,6,6,6-tetrachloro-2,3,3-trimethylhexanoate, b.p.123°-124°/1.0 mm.

B. Ethyl 4,6,6,6-tetrachloro-3-methylhexanoate

1. Using benzoyl peroxide

A mixture of 2.84 g of ethyl 3-methyl-4-pentenoate, 10 ml of carbontetrachloride, and 5 mg of benzoyl peroxide was reacted as described inExample VIII A.1, a total of 20 mg of benzoyl peroxide being addedduring the 20 hours. Distillation of the washed reaction mixture gave3.79 g (63% yield) of ethyl 4,6,6,6-tetrachloro-3-methylhexanoate, b.p.103°-105°/0.4 mm.

Analysis: nmr δ ppm (CCl₄): 4.60-4.30 (m, 1H), 4.11 (q, 2H), 3.25-3.00(m, 2H), 2.75-2.10 (m, 3H), 1.26 (t, 3H), 1.22-0.95 (m, 3H).

2. Using ferric chloride, butylamine and dimethylformamide

Example VIII A.2 was repeated, using 1.42 g of ethyl3-methyl-4-pentenoate instead of the ethyl 2,3,3-trimethyl-4-pentenoate,to give 1.19 g (40% yield) of ethyl4,6,6,6-tetrachloro-3-methylhexanoate, b.p. 110°/0.7 mm.

C. Ethyl 4-bromo-6,6,6-trichloro-2,3,3-trimethylhexanoate

A mixture of 1.70 g (0.01 mole) of ethyl 2,3,3-trimethyl-4-pentenoate, 5ml of bromotrichloromethane, and 50 mg of benzoyl peroxide was refluxedvigorously for 10 hours in an argon atmosphere. The mixture was thendistilled to give 3.0 g (81% yield) of ethyl4-bromo-6,6,6-trichloro-2,3,3-trimethylhexanoate, b.p. 115°-120°/0.5 mm

Analysis: nmr δ ppm (CCl₄): 4.60-3.80 (m, 3H), 3.70-3.10 (m, 2H),3.10-2.70 (m, 1H), 1.60-0.95 (m, 12H).

D. Ethyl 4-bromo-6,6,6-trichloro-3-methylhexanoate

A mixture of 2.84 g of ethyl 3-methyl-4-pentenoate, 5 ml ofbromotrichloromethane and 5 mg of benzoyl peroxide was refluxedvigorously for 6 hours in an argon atmosphere. Then the mixture wascooled, an additional 5 mg of benzoyl peroxide was added and heatingcontinued. After a total of 12 hours, the mixture was cooled, washedsuccessively with water, saturated aqueous sodium bicarbonate, andwater. After drying over magnesium sulfate, the mixture was distilled togive 3.74 g (55% yield) of ethyl4-bromo-6,6,6-trichloro-3-methylhexanoate, b.p. 110°-113°/0.5 mm.

Analysis: nmr δ ppm (CCl₄): 4.65-4.35 (m, 1H), 4.14 (q, 2H), 3.45-3.10(m, 2H), 2.65-2.10 (m, 3H), 1.24 (t, 3H), 1.25-0.95 (m, 3H).

E. Ethyl 4,6,6,6-tetrachloro-2,3-dimethylhexanoate

A mixture of 1.56 g of ethyl 2,3-dimethyl-4-pentenoate, 20 ml of carbontetrachloride, and 20 mg of benzoyl peroxide was charged into a pressurevessel. The vessel was purged with argon, sealed and heated at 140°.After 8 hours, the reactor was cooled, an additional 10 mg of benzoylperoxide was added, heating was resumed for an additional 8 hours, 10 mgof benzoyl peroxide was again added and heating was then continued for atotal of 24 hours. When the reactor had cooled, the contents were washedsuccessively with saturated aqueous sodium bicarbonate, saturatedaqueous sodium chloride and then dried over magnesium sulfate. The driedsolution was distilled to give 1.95 g (63% yield) of ethyl4,6,6,6-tetrachloro-2,3-dimethylhexanoate, b.p. 95°-98°/0.3 mm.

Analysis: nmr ε ppm (CCl₄): 4.52-4.20 (m, 1H), 4.06 (b.q., 2H),3.20-3.00 (m, 2H), 2.75-1.82 (m, 2H), 1.40-0.91 (m, 9H).

In the manner of Example VIII A were prepared:

F. Ethyl 4,6,6,6-tetrachloro-3-phenylhexanoate

b.p. 143°-145°/0.3 mm.

Analysis: nmr δ ppm (CCl₄): 7.50-7.15 (m, 5H), 4.85-4.34 (m, 1H),4.33-3.80 (m, 2H), 3.78-3.42 (m, 1H), 3.40-2.60 (m, 4H), 1.37-0.95 (m,3H).

G. Ethyl 4,6,6,6-tetrachloro-2-methyl-3-phenylhexanoate

b.p. 160°-165°/1.0 mm.

Analysis: nmr δ ppm (CCl₄): 7.45-7.00 (m, 5H), 4.75-4.30 (m, 1H),4.22-2.20 (m, 6H), 1.42-0.64 (m, 6H).

H. Methyl 4,6,6,6-tetrachloro-2-ethyl-3,3-dimethylhexanoate

b.p. 93°-97°/0.2 mm.

Analysis: nmr δ ppm (CCl₄): 4.10 (d.d, 1H), 3.67 (s, 3H), 3.45-2.30 (m,3H), 1.95-1.20 (m, 2H), 1.20-0.70 (m, 9H).

I. Benzyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate

A pressure vessel was charged with 436 mg of benzyl3,3-dimethyl-4-pentenoate in 618 mg of carbon tetrachloride, followed bya mixture of 440 mg of dimethylformamide, 38 mg of ferric chloridehexahydrate and 41 mg of butylamine. The reactor was purged with argon,closed and heated for 8 hours at 120°. The vessel was allowed to cooland the contents were diluted by addition of 50 ml of diethyl ether. Theether solution was washed successively with water, 1N hydrochloric acid,water, saturated aqueous sodium bicarbonate and water. The washedsolution was dried over magnesium sulfate and the solvent was removedunder reduced pressure. The residue was purified by columnchromatography using a silica gel column with benzene as the elutingsolvent to give 470 mg (63% yield) of benzyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate.

Calculated for C₁₅ H₁₈ Cl₄ O₂ : C, 48.42; H, 4.88; Cl, 38.11; Found: C,48.69; H, 5.13; Cl, 38.42.

nmr δ ppm (CCl₄): 7.22 (b.s., 5H), 4.98 (s, 2H), 4.31 (d.d., 1H),3.32-2.80 (m, 2H), 2.58 (d, 1H), 2.28 (d, 1H), 1.17 (s, 3H), 1.08 (s,3H).

J. Using similar techniques, the following compounds can be prepared:

1. ethyl 4,6,6,6-tetrachlorohexanoate

2. ethyl 4,6,6,6-tetrachloro-3-ethyl-3-methylhexanoate

3. ethyl 4,6,6,6-tetrachloro-3-ethyl-3-isopropylhexanoate

4. ethyl 3-t-butyl-4,6,6,6-tetrachloro-3-propylhexanoate

5. ethyl 4,6,6,6-tetrachloro-3,3-diphenylhexanoate

6. ethyl 2-[1-(1,3,3,3-tetrachloropropyl)cyclohexyl]acetate

7. ethyl 4,6,6,6-tetrachloro-3-cyclobutylhexanoate

8. methyl 3-benzyl-4,6,6,6-tetrachlorohexanoate

9. isopropyl 3-benzoyl-4,6,6,6-tetrachlorohexanoate

10. ethyl 3-carbethoxy-4,6,6,6-tetrachlorohexanoate

11. ethyl 3-acetyl-4,6,6,6-tetrachlorohexanoate

12. ethyl 3-butyryl-4,6,6,6-tetrachlorohexanoate

13. ethyl 4,6,6,6-tetrachloro-3-(N,N-dimethylcarboxamido)hexanoate

14. ethyl4,6,6,6-tetrachloro-3-(N-ethyl-N-isopropylcarboxamido)hexanoate

15. ethyl 3-cyano-4,6,6,6-tetrachlorohexanoate

16. ethyl 4,6,6,6-tetrachloro-3-chloromethylhexanoate

17. ethyl 2-benzyl-3-(2-bromoethyl)-4,6,6,6-tetrachlorohexanoate

18. ethyl 4,6,6,6-tetrachloro-3-(1-fluoro-1-methylethyl)hexanoate

19. ethyl 2-benzyl-4-bromo-6,6,6-trichlorohexanoate

20. methyl 6,6,6-trichloro-2-cyclohexyl-4-iodohexanoate

21. ethyl 4,6-dichloro-6,6-difluorohexanoate

22. methyl 4-bromo-6,6,6-trichloro-2,2,3,3-tetramethylhexanoate

23. methyl 4-bromo-6,6,6-trichloro-2-isopropyl-2,3,3-trimethylhexanoate

24. isopropyl 6,6,6-trichloro-4-iodo-2-phenylhexanoate

25. isopropyl6,6-dichloro-6-fluoro-4-iodo-3-methyl-2,2-diphenylhexanoate

26. ethyl 2-carbomethoxy-4,6,6,6-tetrachlorohexanoate

27. ethyl 2-acetyl-4,6,6,6-tetrachloro-3,3-dimethylhexanoate

28. ethyl 2-butyryl-4,6,6,6-tetrachloro-3,3-dimethylhexanoate

29. ethyl 4,6,6,6-tetrachloro-2-(N,N-dimethylcarboxamido)hexanoate

30. ethyl 4,6-dibromo-2-cyano-6,6-difluoro-3,3-dimethylhexanoate

31. ethyl1-(2-bromo-4,4,4-trichloro-1,1-dimethylbutyl)-1-cyclohexanecarboxylate

32. t-butyl 4-bromo-6,6,6-trichloro-2-cyano-3-ethylhexanoate

EXAMPLE IX Direct Synthesis of Ethyl2-(β,β-Dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate from Ethyl4,6,6,6-Tetrachloro-3,3-dimethylhexanoate A. Using potassium t-butoxidein tetrahydrofuran

A solution of 1.8 g (5.8 mmoles) of ethyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate in 2 ml of anhydroustetrahydrofuran was added dropwise to a suspension of 1.3 g (11.6mmoles) of potassium t-butoxide in 20 ml of anhydrous tetrahydrofuran.The mixture was stirred for 1 hour at room temperature. An additional0.65 g (5.8 mmoles) of potassium t-butoxide was then added and themixture was heated under reflux for 2 hours. The mixture was allowed tocool, poured into ice water, and the aqueous mixture was extracted withdiethyl ether. After drying over magnesium sulfate, the ether solutionwas distilled to give 0.93 g (68% yield) of ethyl2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate, b.p.70°-72°/0.1 mm.

B. Using sodium t-butoxide in tetrahydrofuran

A suspension of 2.11 g (0.011 mole) of sodium t-butoxide in 40 ml ofanhydrous tetrahydrofuran was cooled to 0° and to the cold suspensionwas added dropwise a solution of 1.55 g (0.005 mole) of ethyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate in 10 ml of anhydroustetrahydrofuran. When the addition was complete, the mixture was stirredfor 2 hours at about 0°. The cold mixture was neutralized by theaddition of a diethyl ether solution of hydrogen chloride. The solutionwas filtered and the filtrate diluted with diethyl ether. The ethersolution was washed with water, dried over magnesium sulfate anddistilled to give 1.08 g (91% yield) of a mixture of cis and trans ethyl2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate, b.p.63°-66°/0.2 mm. The cis:trans ratio was found by nmr spectroscopicanalysis to be 1:1.

C. Using sodium in ethanol

To a cold solution of 1.01 g (44 moles) of sodium in 80 ml of absoluteethanol was added dropwise, while cooling with ice, 20 ml of an ethanolsolution containing 6.2 g (20 mmoles) of ethyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate. After the addition, themixture was stirred for 1 hour at room temperature, then heated underreflux for 0.5 hour. The mixture was then cooled to 0° and neutralizedby the dropwise addition of hydrogen chloride in ethanol. The neutralmixture was filtered, and the filtrate concentrated to one-tenth itsoriginal volume. The concentrated mixture was diluted with diethylether, and the ethereal solution was washed successively with saturatedaqueous sodium bicarbonate and sodium chloride. The washed solution wasdried over magnesium sulfate and distilled to give 4.47 g (94% yield) ofethyl 2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate, b.p.72°-74°/0.4 mm. The cis:trans distribution was found by gaschromatographic analysis to be 34% cis, 66% trans.

D. Using potassium in ethanol

Twenty milliliters of a solution containing 3.10 g (10 mmoles) of ethyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate in absolute ethanol was addeddropwise, with cooling, to a cold solution of 860 mg (22 mmoles) ofpotassium in 80 ml of absolute ethanol. When the addition was complete,the mixture was stirred for 1 hour at room temperature, then heatedunder reflux for 0.5 hour. The mixture was treated as described inExample IX C to produce 2.30 g (96% yield) of ethyl2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate which wasshown by gas chromatographic analysis to be 26% cis, 74% trans.

E. Using sodium in methanol

Example IX D was repeated using a solution of 575 mg (25 mmoles) ofsodium in 80 ml of absolute methanol, to which was added 20 ml of asolution of 3.1 g (10 mmoles) of ethyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate in absolute methanol. Theproduct was 2.09 g (93% yield) of methyl2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate, b.p.68°-70°/0.2 mm, which was found by gas chromatographic analysis to be23% cis, 77% trans.

F. Using potassium in methanol

Example IX D was repeated using a solution of 860 mg (22 mmoles) ofpotassium in 80 ml of absolute methanol, to which was added 20 ml of asolution of 3.1 g (10 mmoles) of ethyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate in absolute methanol. Theproduct was 2.13 g (95% yield) of methyl2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate which wasfound by gas chromatographic analysis to be 25% cis, 75% trans.

EXAMPLE X Synthesis of Ethyl 6,6,6-Trichloro-3,3-dimethyl-4-hexenoate(an Intermediate X)

Two milliliters of a solution of anhydrous tetrahydrofuran containing709 mg (2 mmoles) of ethyl 4-bromo-6,6,6-trichloro-3,3-dimethylhexanoatewas added dropwise to a suspension of 163 mg (2.4 mmoles) of sodiumethoxide in 20 ml of anhydrous tetrahydrofuran. The mixture was stirredat room temperature for about 16 hours, poured into ice water andextracted with diethyl ether. The extract was dried over magnesiumsulfate and then distilled to give 448 mg (82% yield) of ethyl6,6,6-trichloro-3,3-dimethyl-4-hexenoate, b.p. 83°-85°/0.1 mm.

Analysis: Calculated for C₁₀ H₁₅ Cl₃ O₂ : C, 43.90; H, 5.53; Cl, 38.87;Found: C, 44.12; H, 5.35; Cl, 38.11. nmr δ ppm (CCl₄): 6.13 (q, 2H),4.07 (q, 2H), 2.29 (s, 2H), 1.50-1.00 (m, 9H).

EXAMPLE XI Synthesis of Ethyl 4,6,6-Trichloro-3,3-dimethyl-5-hexenoate(an Intermediate Y) A. From ethyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate

1. Using sodium ethoxide

A solution of 2.04 g of sodium ethoxide in 60 ml of dimethylformamidewas added to a hot solution (140°) of 3.1 g of ethyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate in 20 ml of dimethylformamide.The mixture was maintained at 140° for 2 hours, then cooled to 0°,neutralized with dry hydrogen chloride and poured into ice water. Theaqueous mixture was extracted with ether, and the extract was washedsuccessively with saturated aqueous sodium bicarbonate and sodiumchloride. The washed extract was dried over magnesium sulfate anddistilled to give 1.81 g (77% yield) of ethyl4,6,6-trichloro-3,3-dimethyl-5-hexenoate, b.p. 98°-101°/0.6 mm.

2. Using 1,5-diazabicyclo[3.4.0]nonene-5

A solution of 1.42 g of ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoatein 10 ml of anhydrous dimethylformamide was added dropwise over 0.5 hourto a stirred solution of 1.58 g of 1,5-diazabicyclo[3.4.0]nonene-5 in 10ml of anhydrous dimethylformamide maintained at 0°. The mixture wasstirred for an additional 2 hours, without cooling, poured into icewater, and the aqueous mixture was extracted with diethyl ether. Theether extract was washed with water, dried over magnesium sulfate anddistilled to give a liquid, b.p. 87°-90°/0.12 mm, found by nmr spectralanalysis to consist of 800 mg of ethyl4,6,6-trichloro-3,3-dimethyl-5-hexenoate and 160 mg of ethyl6,6,6-trichloro-3,3-dimethyl-4-hexenoate. The combined yield was 88%.

B. By rearrangement of ethyl 6,6,6-trichloro-3,3-dimethyl-4-hexenoate(an Intermediate X)

1. By heating in tetralin

A solution of 547 mg (2 mmoles) of ethyl6,6,6-trichloro-3,3-dimethyl-4-hexenoate in 2 ml of tetralin was heatedat 150° for 24 hours under an argon atmosphere, then distilled to give356 mg (65% yield) of ethyl 4,6,6-trichloro-3,3-dimethyl-5-hexenoate,b.p. 88°-90°/0.2 mm.

Analysis: Calculated for C₁₀ H₁₅ Cl₃ O₂ : C, 43.90; H, 5.53; Cl, 38.87Found: C, 44.18; H, 5.39; Cl, 38.65

nmr δ ppm (CCl₄): 5.96 (d, 1H), 4.85 (d, 1H), 4.06 (q, 2H), 2.41 (d,1H), 2.23 (d, 1H), 1.23 (t, 3H), 1.11 (s, 6H).

ir (KBr, cm⁻¹): 1735, 1613.

2. By heating in bis(2-methoxyethyl)ether

A solution of 547 mg (2 mmoles) of ethyl6,6,6-trichloro-3,3-dimethyl-4-hexenoate in 2 ml ofbis(2-methoxyethyl)ether (diglyme) was treated as in Example X B.1 togive 383 mg (70% yield) of ethyl4,6,6-trichloro-3,3-dimethyl-5-hexenoate.

3. Heat alone

Ethyl 6,6,6-trichloro-3,3-dimethyl-4-hexenoate (547 mg) was heated at150° for 10 hours under an argon atmosphere, then distilled to give 246mg (45% yield) of ethyl 4,6,6-trichloro-3,3-dimethyl-5-hexenoate, b.p.84°-85°/0.09 mm.

4. Using isobutyric acid

A solution of 547 mg (2 mmoles) of ethyl6,6,6-trichloro-3,3-dimethyl-4-hexenoate and 30 mg of isobutyric acid in2 ml of xylene was refluxed for 6 hours under an argon atmosphere, thendistilled to give 416 mg (76% yield) of ethyl4,6,6-trichloro-3,3-dimethyl-5-hexenoate, b.p. 85°-86°/0.1 mm.

5. Using aluminum chloride

A mixture of 274 mg of ethyl 6,6,6-trichloro-3,3-dimethyl-4-hexenoateand 30 mg of aluminum chloride was stirred at room temperature for 24hours. The mixture was found by gas chromatographic analysis to contain30% ethyl 4,6,6-trichloro-3,3-dimethyl-5-hexenoate.

EXAMPLE XII Synthesis of Ethyl2-(β,β,β-Trichloroethyl)-3,3-dimethylcyclopropanecarboxylate (anIntermediate Z) A. From ethyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate

A solution of sodium t-butoxide was prepared by dissolving 280 mg ofsodium in a mixture of 60 ml of t-butanol and 30 ml of benzene whileprotecting the mixture from moisture. To this solution was added, atroom temperature, 3.1 g (0.01 mole) of ethyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate and the mixture was stirredfor 2 hours. Excess dry hydrogen chloride was added, the mixture wasdiluted with water and extracted with diethyl ether. The ether extractwas washed successively with saturated aqueous sodium bicarbonate andsodium chloride. The washed extract was dried over magnesium sulfate anddistilled to give 2.03 g (74% yield) of ethyl2-(β,β,β-trichloroethyl)-3,3-dimethylcyclopropanecarboxylate, b.p.78°-80°/0.1 mm.

Analysis: Calculated for C₁₀ H₁₅ Cl₃ O₂ : C, 43.90; H, 5.53; Cl, 38.87;Found: C, 43.80; H, 5.41; Cl, 38.87. nmr δ ppm (CCl₄): 4.03 (d.q, 2H),3.1-2.7 (m, 2H), 2.1-1.5 (m, 2H), 1.35 (s, 6H), 1.34 (d.t, 3H).

B. From ethyl 4-bromo-6,6,6-trichloro-3,3-dimethylhexanoate

To a solution of 46 mg of sodium in a mixture of 12 ml of t-butanol and6 ml of benzene was added, at room temperature, 709 mg of ethyl4-bromo-6,6,6-trichloro-3,3-dimethylhexanoate. The mixture was treatedas described in Example XII A to produce 470 mg (86% yield) of ethyl2-(β,β,β-trichloroethyl)-3,3-dimethylcyclopropanecarboxylate.

EXAMPLE XIII Synthesis of Ethyl2-(β,β-Dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate FromIntermediates X, Y and Z A. From ethyl6,6,6-trichloro-3,3-dimethyl-4-hexenoate (an Intermediate X)

A solution of 410 mg of ethyl 6,6,6-trichloro-3,3-dimethyl-4-hexenoatein 1.5 ml of anhydrous tetrahydrofuran was added dropwise with stirringto a suspension of 202 mg of potassium t-butoxide in 20 ml of anhydroustetrahydrofuran. The mixture was heated under reflux with stirring for 3hours, then poured into ice water. The aqueous mixture was extractedwith diethyl ether; the ether extract was dried over magnesium sulfateand distilled to give 281 mg (79% yield) of ethyl2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate, b.p.72°-74°/0.2 mm.

B. From ethyl 4,6,6-trichloro-3,3-dimethyl-5-hexenoate (an IntermediateY)

1. Using sodium in ethanol

A solution of 547 mg (2 mmoles) of ethyl4,6,6-trichloro-3,3-dimethyl-5-hexenoate in 2 ml of ethanol was addeddropwise with stirring to a solution of 57 mg (2.5 mmoles) of sodium in10 ml of absolute ethanol. The mixture was stirred at room temperaturefor 5 hours, cooled with ice and then neutralized by adding a solutionof hydrogen chloride in anhydrous ethanol. The mixture was concentratedto one-tenth its original volume and 50 ml of diethyl ether was added.The mixture was poured into ice water, the layers were separated, andthe ethereal layer was washed successively with saturated aqueous sodiumbicarbonate and sodium chloride. The washed ether solution was driedover magnesium sulfate and distilled to give 436 mg (92% yield) of ethyl2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate, b.p.75°-76°/0.25 mm. Gas chromatographic analysis indicated the cis:transratio to be about 2:8. The nmr spectrum of the trans isomer wasdistinguished by the absorption pattern: (δ ppm; CCl₄) 5.56 (d, 1H),4.05 (b.q., 2H), 2.12 (d.d., 1H), 1.47 (d, 1H), 1.50-1.10 (m, 9H);whereas specific adsorption due to the cis isomer was observed at 6.22(d) and 2.35-2.10 (m).

2. Using sodium t-butoxide in tetrahydrofuran

A solution of 547 mg (2 mmoles) of ethyl4,6,6-trichloro-3,3-dimethyl-5-hexenoate in 2 ml of dry tetrahydrofuranwas added dropwise to a suspension of 288 mg (3 mmoles) of sodiumt-butoxide in 10 ml of dry tetrahydrofuran. The mixture was stirred atroom temperature for 2 hours, then poured into ice water. The aqueousmixture was extracted with diethyl ether, and the ether extract wasdried over magnesium sulfate. The dried extract was distilled to give427 mg (90% yield) of ethyl2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate, b.p.78°-79°/0.35 mm. Gas chromatographic analysis indicated the cis:transratio to be about 1:9.

C. From ethyl2-(β,β,β-trichloroethyl)-3,3-dimethylcyclopropanecarboxylate (anIntermediate Z)

A solution of 2.72 g (0.01 mole) of ethyl2-(β,β,β-trichloroethyl)-3,3-dimethylcyclopropanecarboxylate in 20 ml ofabsolute ethanol was added dropwise to a solution of 250 mg (0.011 mole)of sodium in 80 ml of absolute ethanol. The mixture was heated underreflux for 5 hours, then cooled with ice, and the cold mixture wasneutralized with dry hydrogen chloride. The mixture was concentrated toone-tenth its original volume, then diluted with diethyl ether. Theether solution was washed successively with saturated aqueous sodiumbicarbonate and water. The solution was dried over magnesium sulfate anddistilled to give 1.94 g (82% yield) of ethyl2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate, b.p.75°-76°/0.25 mm.

EXAMPLE XIV Synthesis of Ethyl2-(β,β-Dibromovinyl)-3,3-dimethylcyclopropanecarboxylate A.Dehydrobromination of ethyl 4,6,6,6-tetrabromo-3,3-dimethylhexanoate

Two millileters of an ethanolic solution containing 92 mg (4 mmoles) ofsodium was added dropwise to a cold solution of 1.95 g (4 mmoles) ofethyl 4,6,6,6-tetrabromo-3,3-dimethylhexanoate in 10 ml of absoluteethanol. The cooled mixture was stirred for 2 hours, then poured intochilled 1N hydrochloric acid. The acidic mixture was extracted withdiethyl ether, and the extract was washed successively with saturatedaqueous sodium bicarbonate and sodium chloride. The washed extract wasdried over magnesium sulfate and distilled to give 846 mg (52% yield) ofethyl 4,6,6-tribromo-3,3-dimethyl-5-hexenoate, b.p. 130°-133°/0.3 mm.

Analysis: nmr δ ppm (CCl₄): 6.64 (d, 1H), 4.95 (d, 1H), 4.12 (q, 2H),2.38 (b.d, 2H), 1.4-1.1 (m, 9H).

B. Cyclization of ethyl 4,6,6-tribromo-3,3-dimethyl-5-hexenoate (anIntermediate Y)

A solution of 407 mg (1 mmole) of ethyl4,6,6-tribromo-3,3-dimethyl-5-hexenoate in 1.5 ml of absolute ethanolwas added dropwise to a solution of 30 mg (1.3 mmoles) of sodium in 5 mlof absolute ethanol. The mixture was stirred for 3 hours at roomtemperature, then treated as described in Example XIII A to produce 270mg (83% yield) of ethyl2-(β,β-dibromovinyl)-3,3-dimethylcyclopropanecarboxylate, b.p.95°-98°/0.3 mm.

Analysis: nmr δ ppm (CCl₄): 6.70, 6.07 (d, 1H), 4.05 (q, 2H), 2.45-1.40(m, 2H), 1.35-1.10 (m, 9H). ir (KBr, cm⁻¹): 1725, 1223, 1175, 855, 800,762.

EXAMPLE XV Synthesis of Other 2-Dihalovinylcyclopropanecarboxylates A.Ethyl 2-(β,β-dichlorovinyl)-1,3,3-trimethylcyclopropanecarboxylate

1. From ethyl 4,6,6,6-tetrachloro-2,3,3-trimethylhexanoate

A solution of 1.3 g (4 mmoles) of ethyl4,6,6,6-tetrachloro-2,3,3-trimethylhexanoate in 5 ml of anhydrous1,2-dimethoxyethane was added dropwise to a suspension of 500 mg (10mmoles) of 50% sodium hydride in 15 ml of the same solvent. The mixturewas heated for 20 hours under reflux, then allowed to cool. The reactionmixture was neutralized by the addition of 1N hydrochloric acid andextracted with diethyl ether. The extract was washed with saturatedaqueous sodium chloride, dried over magnesium sulfate and distilled togive 550 mg (55% yield) of ethyl2-(β,β-dichlorovinyl)-1,3,3-trimethylcyclopropanecarboxylate, b.p.71°-76°/0.08 mm.

The nmr spectrum of the product indicated that it consisted of 30% cisand 70% trans isomers. The trans isomer was distinguished by theadsorption peaks (δ, ppm, CCl₄): 5.57 (d, 2H), 4.10 (b.q, 2H), 2.28 (d,2H), 1.40-0.90 (m, 12H), while the cis isomer was distinguished by theabsorption (δ, ppm. CCl₄): 6.26 (d, 2H) and 1.52 (d, 2H).

Analysis: nmr δ ppm (CCl₄): 6.26-5.57 (d, 1H), 4.10 (b.q, 2H), 2.28-1.52(d, 1H), 1.40-0.90 (m, 12H).

2. From ethyl 4-bromo-6,6,6-trichloro-2,3,3-trimethylhexanoate

A solution of 368.5 mg (1 mmole) of4-bromo-6,6,6-trichloro-2,3,3-trimethylhexanoate in 1 ml of anhydroustetrahydrofuran was added dropwise to a suspension of 224 mg (2 mmoles)of potassium t-butoxide in 10 ml of anhydrous tetrahydrofuran. Themixture was heated for 5 hours under reflux, poured into ice water, andthe aqueous mixture was extracted with diethyl ether. The ether extractwas dried over magnesium sulfate and distilled to give 55 mg (22% yield)of ethyl 2-(β, β-dichlorovinyl)-1,3,3-trimethylcyclopropanecarboxylate.

3. Via ethyl 6,6,6-trichloro-2,3,3-trimethyl-4-hexenoate (anIntermediate X)

A solution of 737 mg of ethyl4-bromo-6,6,6-trichloro-2,3,3-trimethylhexanoate in 20 ml of anhydroustetrahydrofuran was cooled to 0°. To the cold solution was added 163 mgof sodium ethoxide and the mixture was stirred for 5 hours. The cooledmixture was poured into cold 1N hydrochloric acid and extracted withdiethyl ether. The ether extract was washed successively with water,saturated aqueous sodium bicarbonate and aqueous sodium chloride, thendried over magnesium sulfate. The dried ether extract was distilled togive 430 mg (75% yield) of ethyl6,6,6-trichloro-2,3,3-trimethyl-4-hexenoate, b.p. 92°-95°/0.2 mm.

Analysis: nmr δ ppm (CCl₄): 6.15 (q, 2H), 4.07 (q, 2H), 2.70-2.10 (m,1H), 1.30-0.90 (m, 12H).

Two milliliters of an anhydrous 1,2-dimethoxyethane solution containing547 mg of ethyl 6,6,6-trichloro-2,3,3-trimethyl-4-hexenoate was addeddropwise to a suspension of 168 mg of 50% sodium hydride in 10 ml ofanhydrous 1,2-dimethoxyethane. The mixture was heated under reflux for12 hours, allowed to cool to room temperature, then neutralized by theaddition of an anhydrous solution of hydrogen chloride in diethyl ether.The neutralized mixture was poured into ice water and extracted withdiethyl ether. The extract was dried over magnesium sulfate anddistilled to give 308 mg (65% yield) of ethyl2-(β,β-dichlorovinyl)-1,3,3-trimethylcyclopropanecarboxylate, b.p.75°-80°/0.2 mm.

4. Via ethyl 4,6,6-trichloro-2,3,3-trimethyl-5-hexenoate (anIntermediate Y)

A mixture of 288 mg of ethyl 6,6,6-trichloro-2,3,3-trimethyl-4-hexenoate(an Intermediate X) and 30 mg of phenol in 1 ml of xylene was refluxedfor 10 hours under an argon atmosphere. Distillation gave 196 mg (68%yield) of ethyl 4,6,6-trichloro-2,3,3-trimethyl-5-hexenoate, b.p.91°-93°/0.12 mm.

Analysis: nmr δ ppm (CCl₄): 5.95-5.94 (d, 1H), 4.77-4.62 (d, 1H),4.03-4.02 (q, 2H), 2.80-2.35 (m, 1H), 1.35-0.90 (m, 12H).

A solution of 575 mg (2 mmoles) of ethyl4,6,6-trichloro-2,3,3-trimethyl-5-hexenoate in 5 ml of anhydrous1,2-dimethoxyethane was added dropwise to a dispersion of 120 mg (2.5mmoles) of 50% sodium hydride in 10 ml of anhydrous 1,2-dimethoxyethane.The mixture was heated under reflux for 5 hours, then cooled. The cooledmixture was neutralized with 1N hydrochloric acid and extracted withdiethyl ether. The ether extract was washed successively with saturatedaqueous sodium bicarbonate and sodium chloride. The washed extract wasdried over magnesium sulfate, then distilled to give 360 mg (72% yield)of ethyl 2-(β,β-dichlorovinyl)-1,3,3-trimethylcyclopropanecarboxylate,b.p. 75°-78°/0.1 mm.

B. Ethyl 2-(β,β-dichlorovinyl)-3-methylcyclopropanecarboxylate

1. From ethyl 4,6,6,6-tetrachloro-3-methylhexanoate

A solution of 592 mg of ethyl 4,6,6,6-tetrachloro-3-methylhexanoate in 5ml of absolute ethanol was added dropwise with stirring to a solution of69 mg of sodium in 15 ml of absolute ethanol. After 5 hours the mixturewas refluxed for 2 hours, then allowed to cool to room temperature, andneutralized by the addition of a solution of hydrogen chloride inanhydrous diethyl ether. The mixture was poured into ice water,extracted with diethyl ether, and the ether extract was dried overmagnesium sulfate. The dried solution was distilled to give 292 mg (66%yield) of ethyl 2-(β,β-dichlorovinyl)-3-methylcyclopropanecarboxylate,b.p. 70°-77°/0.5 mm.

Analysis: ir (KBr, cm⁻¹): 3040, 1725, 1615, 1190, 1045, 922, 883, 861,824, 645.

2. From ethyl 4-bromo-6,6,6-trichloro-3-methylhexanoate

A solution of 681 mg of ethyl 4-bromo-6,6,6-trichloro-3-methylhexanoatewas treated as described immediately above to produce 276 mg (62% yield)of ethyl 2-(β,β-dichlorovinyl)-3-methylcyclopropanecarboxylate, b.p.66°-72°/0.3 mm.

3. From ethyl 6,6,6-trichloro-3-methyl-4-hexenoate (an Intermediate X)

One milliliter of a solution of 259.5 mg of ethyl6,6,6-trichloro-3-methyl-4-hexenoate in anhydrous ethanol was addeddropwise to a solution of 46 mg of sodium in 10 ml of the same solvent.The mixture was heated under reflux for 3 hours, allowed to cool, thenneutralized by adding an ethereal solution of dry hydrogen chloride inether. The neutralized mixture was poured into ice water and extractedwith ether. The extract was dried over magnesium sulfate and distilledto give 156 mg (70% yield) of ethyl2-(β,β-dichlorovinyl)-3-methylcyclopropanecarboxylate, b.p. 62°-66°/0.3mm.

C. Ethyl 2-(β,β-dichlorovinyl)-3-phenylcyclopropanecarboxylate

In the manner of Example XV B.1, 716 mg of ethyl4,6,6,6-tetrachloro-3-phenylhexanoate was reacted to obtain 274 mg (48%yield) of ethyl 2-(β,β-dichlorovinyl)-3-phenylcyclopropanecarboxylate,b.p. 105°-115°/0.1 mm. The nmr spectrum of the product indicated that itconsisted of a mixture of isomers; the prominent nmr absorptions were asfollows:

nmr δ ppm (CCl₄): 7.20 (m, 5H), 6.10 (b.d, 0.5H), 5.13 (d, 0.5H), 4.17(b.q, 2H), 3.10-2.00 (m, 3H), 1.32 (b.t, 3H).

D. Benzyl 2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate

A solution of 335.7 mg of benzyl4,6,6,6-tetrachloro-3,3-dimethylhexanoate in 2 ml of anhydroustetrahydrofuran was added dropwise to a suspension of 192 mg of sodiumt-butoxide in 8 ml of anhydrous tetrahydrofuran at 0°. The mixture wasstirred for 2 hours at 0°, then for 0.5 hour at room temperature. Themixture was neutralized by adding a solution of dry hydrogen chloride inether. The neutral solution was washed with water, then dried overmagnesium sulfate. The dried solution was distilled to give 210 mg (77%yield) of benzyl2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate, b.p.114°-118°/0.13 mm.

Analysis: Calc'd for C₁₅ H₁₆ Cl₂ O₂ : C, 60.22; H, 5.39; Cl, 23.70;Found: C, 60.12; H, 5.39; Cl, 23.90; nmr δ ppm (CCl₄): 7.22 (b.s., 5H),6.18 (d, 0.5H), 5.50 (d, 0.5H), 5.01 (s, 2H), 2.4-1.5 (m, 2H), 1.42-1.05(m, 6H).

E. The following compounds can be prepared by similar methods:

1. ethyl 2-(β,β-dichlorovinyl)cyclopropanecarboxylate

2. ethyl 3-benzyl-2-(β,β-dichlorovinyl)cyclopropanecarboxylate

3. ethyl2-(β,β-dichlorovinyl)-3-isopropyl-3-methylcyclopropanecarboxylate

4. ethyl1-benzoyl-3-(2-butenyl)-2-(β,β-dichlorovinyl)-3-ethylcyclopropanecarboxylate

5. methyl 2-(β,β-dichlorovinyl)-3-methyl-3-phenylcyclopropanecarboxylate

6. ethyl 2-(β,β-dichlorovinyl)spiro[2.5]octane-1-carboxylate

7. methyl3-allyl-3-carbomethoxy-2-(β,β-dichlorovinyl)cyclopropanecarboxylate

8. methyl3-carbomethoxy-2-(β,β-dichlorovinyl)-3-cyanocyclopropanecarboxylate

9. ethyl3-acetyl-1-benzyl-2-(β,β-dichlorovinyl)-1-cyclohexyl-3-ethylcyclopropanecarboxylate

10. methyl3-benzoyl-2-(β,β-dibromovinyl)-3-phenylcyclopropanecarboxylate

11. ethyl3-acetyl-2-(β,β-dibromovinyl)-3-(N,N-dimethylcarboxamido)cyclopropanecarboxylate

12. ethyl 3-cyano-2-(β,β-difluorovinyl)-3-methylcyclopropanecarboxylate

13. ethyl2-(β,β-dichlorovinyl)-1-ethyl-3,3-dimethylcyclopropanecarboxylate

14. propyl 2-(β-bromo-β-chlorovinyl)-1,3-dimethylcyclopropanecarboxylate

15. methyl2-(β,β-difluorovinyl)-3,3-dimethyl-1-phenylcyclopropanecarboxylate

16. ethyl1-vinyl-2-(β,β-dichlorovinyl)-3-cyclohexyl-3-ethylcyclopropanecarboxylate

17. methyl1-carboisopropoxy-2-(β,β-dibromovinyl)-3,3-dimethylcyclopropanecarboxylate

18. ethyl1-acetyl-2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate

19. methyl 1-butyryl-2-(β,β-dichlorovinyl-3-cyanocyclopropanecarboxylate

20. ethyl2-(β,β-dibromovinyl)-1-(N,N-dimethylcarboxamido)-3-methylcyclopropanecarboxylate

21. methyl 1-cyano-2-(β,β-difluorovinyl)-3-phenylcyclopropanecarboxylate

22. ethyl1-ethynyl-2-(β,β-dichlorovinyl)-3,3-dimethylcyclopropanecarboxylate

EXAMPLE XVI Synthesis of Cyclopropanecarboxylates Containing Otherβ-Substituents A. Preparation of ethyl1,3,3-trimethyl-2-vinylcyclopropanecarboxylate

1. A mixture of 920 mg (5 mmoles) of ethyl 2,3,3-trimethyl-4-hexenoate,10 ml of carbon tetrachloride, 107 mg (6 mmoles) of N-bromosuccinimide,and 50 mg of benzoyl peroxide was heated under reflux for about twohours. The insoluble succinimide was removed by filtration. The filtratewas washed successively with saturated aqueous sodium bicarbonatesolution and water, then dried over magnesium sulfate. The driedsolution was distilled to give 1.14 g (86% yield) of ethyl6-bromo-2,3,3-trimethyl-4-hexenoate, b.p. 80°-81°/0.8 mm.

Analysis: nmr δ ppm (CCl₄): 5.84-5.37 (m, 2H), 4.01 (q, 2H), 3.85 (d,2H), 2.24 (q, 1H), 1.22 (t, 3H), 1.13-0.97 (m, 9H).

2. A solution of 526 mg (2 mmoles) of ethyl6-bromo-2,3,3-trimethyl-4-hexenoate in 2 ml of anhydrous tetrahydrofuranwas added dropwise to a suspension of 224 mg (2 mmoles) of potassiumt-butoxide in 10 ml of tetrahydrofuran. The mixture was heated underreflux for two hours and then allowed to cool to room temperature. Anadditional 116 mg (1 mmole) of potassium t-butoxide was added, and themixture again heated under reflux for two hours. The reaction mixturewas poured into ice water, and the aqueous mixture extracted withdiethyl ether. The ether extract was dried over magnesium sulfate anddistilled to give 200 mg (55% yield) of ethyl1,3,3-trimethyl-2-vinylcyclopropanecarboxylate, b.p. 92°-95°/1.5 mm.

Analysis: nmr δ ppm (CCl₄): 6.40-4.80 (m, 3H), 4.03 (b.q, 2H), 2.08(b.d, 1H), 1.40-1.00 (m, 12H).

B. Preparation of ethyl 3,3-dimethyl-2-vinylcyclopropanecarboxylate

1. By the method of Example XVI-A1 there was prepared ethyl6-bromo-3,3-dimethyl-4-hexenoate, b.p. 85°/0.5 mm.

Analysis: ir (cm⁻¹): 1730, 1365, 1215, 1033, 970, 710, 590.

2. By the method of Example XVI-A2 ethyl6-bromo-3,3-dimethyl-4-hexenoate was converted to ethyl3,3-dimethyl-2-vinylcyclopropanecarboxylate, b.p. 68°-75°/25 mm.

Analysis: ir (cm⁻¹): 1728, 1630, 1187, 1148, 1097, 1030, 990, 902.

We claim:
 1. A process for preparing a halovinylcyclopropanecarboxylateof the formula ##STR9## which comprises (i) adding a carbon halide,MCX₃, to a γ-unsaturated carboxylate of the formula ##STR10## to producea γ-halocarboxylate of the formula ##STR11## (ii) dehydrohalogenatingthe γ-halocarboxylate to remove therefrom two molecules of hydrogenhalide so as to bring about ring closure between and α and γ carbons andform a double bond between the δ and ε carbons to produce saidhalovinylcyclopropanecarboxylate;wherein (a) R is a lower alkyl group;(b) X is a halogen atom; (c) M is a monovalent substituent which ishalogen, hydrogen, lower alkyl, or lower haloalkyl; and (d) MCX₃ is apolyhalogenated lower alkane.
 2. A process as in claim 1 in which the Xatoms removed in the dehydrohalogenation step (ii) are selected fromchlorine and bromine atoms.
 3. A process as in claim 2 in which the Xatoms removed are chlorine atoms and the dehydrohalogenation is effectedby reacting the γ-halocarboxylate with an alkali metal alkoxide in asolvent.
 4. A process for preparing a halovinylcyclopropanecarboxylateof the formula ##STR12## which comprises dehydrohalogenating aγ-halocarboxylate of the formula ##STR13## to remove therefrom twomolecules of hydrogen halide so as to bring about ring closure betweenthe α and γ carbons and form a double bond between the δ and ε carbonsto produce said halovinylcyclopropanecarboxylate;wherein (a) R is alower alkyl group; (b) X is a halogen atom; and (c) M is a monovalentsubstituent which is halogen, hydrogen, lower alkyl, or lower haloalkyl.5. A process as in claim 4 in which the X atoms removed in thedehydrohalogenation are selected from bromine and chlorine atoms.
 6. Aprocess as in claim 5 in which the X atoms removed are chlorine atomsand the dehydrohalogenation is effected by reacting theγ-halocarboxylate with an alkali metal alkoxide in a solvent.